Intravascular Lithotripsy: The State of the Technology

Intravascular lithotripsy (IVL), a novel therapy designed to treat calcified artery disease, is quickly proving itself to be a new star player in the cardiovascular device space. Heads turned across the medical device industry last year when the first commercially approved intravascular lithotripsy device, made by Shockwave Medical, was acquired by Johnson & Johnson for $13 billion. While the price tag may seem staggering, the acquisition has a good chance of quickly achieving a return on investment as J&J reported 25% quarterly revenue growth (over the previous year) for this business unit in their Q4 earnings call. 

The Shockwave acquisition, however, marks only the tip of the iceberg in an emerging marketplace. IVL technology has been in development for nearly a decade with several large medical device manufacturers and independent startups developing various versions of this technology. 

Prior to an FDA-approved IVL device, there were a handful of common means for treating calcified arteries. These options included using a non-compliant, high-pressure or scoring balloon; rotational or orbital atherectomy, which uses high-speed rotating burrs to drill through and grind up the calcified plaque; or excimer laser atherectomy systems, which deliver ultraviolet light pulses to essentially vaporize the calcified plaque through photochemical ablation. Risks associated with these methods include chances of blood vessel damage such as perforations, which are among the most difficult complications to manage, or a general inability to achieve the desired luminal gain in order to keep the artery open long-term. 

Technology Profile

IVL, which generally harnesses energy waves to break apart calcifications, offers a safer, less aggressive method to restore healthy blood flow with reduced chances of complications. Further, once the calcified lesions have been fractured or modified and the vessel is much more pliable, IVL methods can support easier placement of drug-coated balloons or stents that will enable maximum luminal gain to restore blood flow to the affected area over time.

Recent studies have indicated that varying IVL methods (including those still in development) have better patient outcomes than previously popular atherectomies and cutting balloons. In general, IVL modalities offer a lower risk of dissection than balloon angioplasty, are more effective at treating heavily calcified arteries, are less invasive than surgical options, and are easier to use than non-IVL modalities such as rotational, orbital, or laser atherectomy. Legacy modalities are still being used in the field today, though with less frequency since the availability of IVL devices, as documented by the National Cardiovascular Data Registry¹ (Figure 1). 

IVL Players

The first commercially available device, Shockwave IVL, works by emitting electrical or acoustic energy. The energy is generated through electrodes or emitters located inside a small balloon that is placed within the calcified vessel. These emitters produce high-energy electrical sparks that generate vapor bubbles in the fluid within the balloon. When the vapor bubbles rapidly expand and collapse violently, this creates high-pressure shockwaves, which target calcium deposits without damaging the healthy soft tissue. 

The quick adoption of the first-to-market IVL device is extremely promising for additional market players. So too are the various mechanisms of action and new clinical proof of several up-and-coming devices accelerating toward the commercial marketplace, from enhancements to the electrical or acoustic method to a new hydraulic-based option. 

One such innovation exploring acoustic and laser energy for IVL is Bolt Medical. The Bolt IVL system uses laser energy transmitted through optical fibers, creating a plasma event that is then converted into acoustic pressure waves to fracture calcium deposits, similar to the Shockwave device. A secondary cavitation bubble further fractures the calcium to maximize vessel compliance. Bolt has treated 95 patients as part of its RESTORE ATK (above the knee) pivotal trial, 20 patients as part of its RESTORE BTK (below the knee) pivotal trial, and 33 patients as part of its RESTORE FIH (first-in-human) Coronary study. All patients in all three studies were treated at sites outside the United States. Lastly, Bolt commenced its RESTORE Coronary pivotal study in 2024 outside the U.S. but has not enrolled any U.S. patients at the time of print.

Some possible drawbacks of a system using acoustic and laser energy may be the cost and service burden of the laser capital platform and the lack of differentiation to the Shockwave device, which may cause delays in FDA clearance. Notably, Boston Scientific announced an agreement to acquire Bolt Medical in early 2025 for up to nearly $900M, pending certain regulatory milestones.

An alternative device that also uses electrodes like the Shockwave platform is in development by Fastwave Medical, which claims to have a more predictable sonic output with increased pulse availability, ensuring consistent energy delivery to target various types of calcified lesions. Fastwave completed a first-in-human trial of the device for peripheral indications, treating nine lesions in eight patients in Mexico, and has also reported the development of a separate, laser-based platform for coronary applications.

Abbott Laboratories stated in late January that it would be commencing a coronary trial of its own, using an IVL device developed by Cardiovascular Systems Inc. (CSI), which it acquired in 2023. This platform is another electrical and acoustic-based technology for which clear differentiation from Shockwave, Bolt, and Fastwave platforms remains to be seen.

Though classified as an atherectomy study, Philips is also claiming to be in the IVL playing field with its trial using a unique laser atherectomy and laser-based IVL combination catheter device. This study is exploring treatment in peripheral cases and will enroll up to 155 patients in the U.S.

Among the sea of electrical and acoustic pulse devices are those that employ more unique mechanisms of action, such as Amplitude Vascular Systems (AVS), which leverages hydraulic pressure pulses to achieve calcium fracture. The Pulse IVL device uses pressurized CO₂ to create very brief, high-pressure peaks that pulsate 15 times per second more uniformly throughout the balloon length compared to one or two pulses per second radiating directly from the emitter locations seen in some electrical-based versions. 

The AVS Pulse IVL platform allows for the delivery of up to 5,000 total pulses, over 12 times the current commercially available technology, making it a great option for long- or multi-vessel disease. Since they do not require electrodes or emitters, hydraulic-based devices can achieve much lower crossing profiles and better distal flexibility—an advantage for treating more challenging anatomies. 

AVS completed its POWER PAD I FIH study in 2023 in Australia and the Dominican Republic and started enrolling for its POWER PAD II U.S. IDE study in 2024, which will explore peripheral use and enroll up to 120 patients in the U.S. AVS leaders have also expressed their interest in pursuing coronary and carotid artery indications. 

Commercial Landscape

Aside from considering the upcoming variations in IVL technology, it is also important to discuss the current reimbursement landscape. Shockwave has done an excellent job in establishing payment pathways for both peripheral and coronary applications. Long-term reimbursement codes came into effect starting in 2022 and 2023 for peripheral and coronary applications, respectively, that provided a $5,000 to $6,000 and $8,000 average nationwide increase for peripheral and coronary procedures, respectively.

Joining the IVL development game has never been more attractive. While Shockwave currently enjoys a head start in the commercial IVL space globally, international manufacturers and start-ups alike are in various stages of clinical trials for new IVL devices to join them. As different devices suited for certain indications or calcification treatment challenges become more widely available, the utilization for IVL stands to far exceed that of prior methods for treating calcified arterial disease, perhaps even tackling lesion-specific approaches beyond peripheral, coronary, and carotid applications.

Reference

1. tinyurl.com/mpo250431

Robert Chisena, Ph.D., is the co-founder and CTO of AVS. He leads research and product development. Dr. Chisena founded Amplitude Vascular Systems in 2019 with Hitinder Gurm, with whom he worked while completing his Ph.D. in mechanical engineering at the University of Michigan. Prior to completing his doctorate, Dr. Chisena studied mechanical engineering at Pennsylvania State University (BS). His research encompasses a vast area of both biomedical science and design, including medical device manufacturing, cardiovascular mechanics, and safety and efficacy studies of diseased tissue. Dr. Chisena is named as an inventor on five patents.