Treating calcific coronary artery disease remains a significant challenge, despite advancements in various technologies.1 The main difficulty with calcium in coronary artery disease lies in achieving optimal stent expansion, with suboptimal results often arising when adequate expansion is not achieved.2
Core laboratory analyses of drug-eluting stent studies suggest that angiographic/visual assessments frequently underestimate the presence of calcium. Pooled data indicate moderate to heavy calcification in nearly 26% of cases.3 Studies using intravascular imaging reveal calcific arcs of <180° in 24.5% of cases, with an additional 24.5% showing arcs of 180–270°.4,5 This highlights that eccentric calcium is present in half of all cases.
Intravascular lithotripsy (IVL), introduced to the UK in 2018, was a welcome addition to the armamentarium for managing calcific coronary disease. Its simplicity, compared with debulking technologies, such as rotational, orbital and laser atherectomy, has driven its adoption.6 However, there is an opportunity for the interventional community to reassess the understanding and use of this technology.
This expert opinion article aims to refine our knowledge of IVL mechanistic properties, emphasising that it is not a balloon angioplasty tool, but a therapy delivery system using a balloon. The technical aspects of IVL and its application in calcific coronary disease will be explored, along with lessons from its use in peripheral vascular interventions to enhance its utility in coronary applications. Suggested refinement in IVL application is introduced based on the evidence and experience of the authors
Current Usual Practice and Its Limitations
IVL was initially positioned as an effective tool for concentric calcium. IVL emitters produce electric sparks that create vapour bubbles in the surrounding fluid medium within the integrated balloon. A low level of electric energy leads to the formation and rapid expansion of vapour bubbles. This results in acoustic pressure waves that radiate circumferentially and transmurally in an unfocused manner. IVL shock waves propagate through soft tissue with minimal effect, but the leading edge imparts compressive stress against calcium, which leads to calcium fracture. Reflected sound waves then deepen and intersect these fractures, modifying the calcium and improving vessel compliance.6,7 This dual action ensures comprehensive calcium modification, making the vessel more compliant for optimal stent deployment.
The straightforward explanation of this mechanism, along with its established use in kidney stone treatment, facilitated its acceptance. The standard recommendation was to de-air and inflate the balloon to 4 atm to deliver therapy, followed by increasing to 6 atm for assessing vessel compliance.7 Thorough de-airing is particularly important, as introduction of air within the IVL balloon will reduce the energy delivery, as shown in seminal work on intravascular lithotripsy in other fields (Figure 1A).8,9 This guidance led some interventionalists to treat IVL as an extension of balloon angioplasty, focusing also on hydrostatic pressure rather than considering the balloon only as an aid to deliver therapy. The role of the balloon in this modality is to ensure that there is a fluid interface covering the emitters to facilitate energy delivery and avoid ‘dry shocks’, which can lead to complications, such as balloon rupture.9 Over time, a better understanding has clarified that the 4-atm inflation is not a nominal pressure, but a means to prevent dry shocks, with minimal inflation pressures to ensure fluid coverage of emitters is sufficient.
Higher pressures do not increase energy delivery, and as per the inverse square law, might reduce overall energy delivered, and also increase the risk of balloon damage.7 IVL balloons are often sized based on the distal vessel diameter in tapering long lesions and to the daughter vessel in bifurcations. This is due to concerns about safety and deliverability of IVL balloons based on our approach to conventional balloon angioplasty. However, if the IVL balloons are used at the recommended pressure, sound waves traverse through non-calcific tissue without causing any damage. Also, the crossing profile of the IVL balloons is largely determined by the presence of the emitters rather than the balloon size (e.g. 0.043 in for 2.5 mm versus 0.046 in for 4.0 mm).10 All these factors limit the efficacy of the technology in the event of undersizing of the IVL balloon (Figure 1B).
Positioning the IVL catheter correctly is critical for ensuring effective calcium modification.7 Each emitter’s placement relative to the radiopaque markers can influence the distribution of therapy. Specifically, the proximal emitter is located approximately 2 mm distal to the proximal radiopaque marker, while the distal emitter is positioned 4 mm proximal to the distal radiopaque marker (Figure 1C). Understanding this arrangement can help operators align the catheter more precisely, ensuring optimal therapy delivery. Use of advanced fluoroscopy (e.g. ClearStent or StentBoost) can be helpful in positioning the emitters in the intended areas, as demonstrated in previous studies.11 Misalignment or failure to ensure overlap between balloon positions risks geographic miss of effective energy delivery, compromising treatment efficacy.7
Perceived Conceptual Challenges in Using Intravascular Lithotripsy Catheter in Eccentric and Nodular Coronary Calcifications, and Potential Learning from the Vascular Usage of Intravascular Lithotripsy Catheters
Initial scepticism about IVL’s efficacy in eccentric and nodular calcium stemmed from concerns about limited sound wave reflection, thus potentially limiting its calcium modulation abilities. However, the DISRUPT CAD studies demonstrated similar stent expansion in both nodular and non-nodular calcium, as well as between eccentric and concentric calcium.12,13 These findings underscored the potential efficacy of IVL in these challenging scenarios.
Data from peripheral vascular applications, such as the DISRUPT PAD II study, revealed benefits of 10% balloon oversizing, including improved patency and reduced target lesion revascularisation.14 Oversizing, performed at 2–4 atm, increased calcium modification and maintained safety.15 These insights may be extrapolated to coronary applications. It is important, however, to acknowledge the differences between the coronary and peripheral IVL technology, including smaller and shorter balloons, fewer emitters, and different emitter locations in the coronary IVL catheters compared with the peripheral equivalent.16 Nonetheless, the basis of energy generation and impact on calcium is similar, and therefore, extrapolation of peripheral IVL may be of value in the coronary sphere.
In nodular and eccentric calcium, traditional scoring and cutting balloons pose risks, such as dissections and perforations, especially in non-calcified regions.17 In contrast, IVL’s sound waves safely traverse soft tissues without causing injury. Fractures induced by IVL therapy often occur at tissue interfaces, enhancing vessel compliance and enabling optimal stent expansion.7 This highlights IVL’s unique safety profile compared with other balloon-based technologies, although we acknowledge that no head-to-head comparison studies exist for IVL versus scoring/cutting balloons.
Unlike conventional balloon angioplasty, the approach of placing the middle of the IVL balloon on the nodular calcium with 1:1 balloon sizing inflated at 4 atm can render the technology less effective, as it can potentially reduce the alignment of the emitters to the base of the nodule, and may even lead to less contact of the balloon edges with the vessel wall at the area of interest, as illustrated in Figure 2A. Additionally, despite evidence that the number of cycles of therapy correlates to more calcium fractures, it remains unclear whether more cycles of therapy are required in eccentric and nodular calcium compared with concentric calcium to ensure effective lesion modification.18
Proposed Iterations of Using Intravascular Lithotripsy Therapy in Various Calcified Coronary Artery Disease
Concentric Tight Calcified Lesions
Current 1:1 balloon sizing remains effective. However, balloons should be sized to the proximal vessel diameter, especially in tapering lesions. A 10% oversizing (0.5 mm) and delivering therapy at 2–4 atm may enhance efficacy while maintaining safety. This approach ensures uniform energy delivery and calcium modification across the lesion. Furthermore, maintaining low-pressure inflation throughout the lesion length reduces the risk of balloon failure. Nonetheless, this is based on expert opinion, and prospective studies are required to provide objective evidence on safety and efficacy over balloon oversizing with low-pressure inflation in the coronary setting.
Large Bifurcations
In our experience, balloons should be sized to the parent vessel diameter and placed across the bifurcation, delivering therapy at 2 atm. This approach simultaneously modifies calcium in both the parent and daughter vessels, and any calcium at the ostium of the side branch, thus subsequently facilitating side branch access and lesion preparation at the ostium of the side branch (Figure 2B). Ensuring adequate overlap and therapy delivery across the bifurcation improves stent deployment and reduces complications, in our experience. If both limbs of the bifurcation need calcium modulation, it is recommended to first use the IVL catheter in the more angulated daughter branch, to enable likely successful delivery of the IVL catheter in both branches. By preparing the lesion more comprehensively, operators can avoid the risk of under-deployment, which is critical in bifurcated vessels. We acknowledge, however, that prospective IVL bifurcation studies, of which there are none currently, are needed to provide evidence on the safety and clinical effectiveness of our proposed use of IVL in bifurcations.
Nodular and Eccentric Calcium
Oversizing by 0.5 mm and inflating at 2 atm creates a ‘pillowing effect’, a term used by the authors to describe the hypothesis of a softer balloon assuming the shape of eccentric calcium, thereby ensuring adequate contact and calcium modification. Balloons should be advanced distally and withdrawn with 2 mm overlap to avoid geographic miss. This technique accentuates fractures at weak points, improving vessel compliance (Figure 3A). The ‘pillowing effect’ is hypothesised to also ensure all aspects of calcific nodules (ascending and descending rims, summit of the nodule, and the transition areas of the rims to the adjacent calcific plates) are modified (Figure 3B), thus enabling optimal lesion preparation. These fractures often form at transition zones in calcium thickness, helping to dismantle rigid calcium structures and prepare the lesion for stenting (Figures 4 and 5).
Relevant to all applications of IVL described above, we stress the importance of using intravascular imaging where possible to define the nature of the disease, confirm modification and optimise stent results, as per the latest evidence in calcified coronary disease.19 Future studies on IVL testing the hypothesis described in this expert opinion should also use intravascular imaging to illustrate mechanistic implications of proposed IVL use. Moreover, the proposed hypothesis of pillowing requires prospective studies to demonstrate its efficacy and safety in the coronary setting. Finally, studies addressing potential differences in IVL effectiveness by inflation pressure (e.g. 2 versus 6 atm) may provide more guidance as to the optimal use of IVL in eccentrically calcified coronary disease.
Conclusion
Since its introduction in 2018, understanding and usage of IVL technology has evolved. Emphasising de-airing and recognising that 4 atm is not a nominal pressure, but a mechanism to prevent dry shocks, can optimise therapy delivery. Oversizing balloons by 0.5 mm and using lower pressures (2 atm) can enhance efficacy, particularly in nodular, eccentric and bifurcated lesions.
Given IVL’s safety in soft tissues, slightly overshooting balloon size can ensure comprehensive calcium modification by enabling breaks in zones of transitions from thicker to thinner calcium and from superficial to deep calcium. Renaming the technology as an ‘IVL catheter’ rather than ‘IVL balloon’ may correct misconceptions, facilitating its optimal application across calcific coronary disease, including concentric rings, nodules, eccentric lesions and plates.
This nuanced understanding of IVL, bolstered by lessons from peripheral vascular studies, positions the technology as a versatile tool for tackling complex calcific coronary artery disease across the spectrum. Future studies and real-world data will likely refine these approaches further, solidifying IVL’s role in interventional cardiology.