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Intravascular imaging–guided intracoronary lithotripsy: First real‐world experience

Abstract Background and Aims Coronary calcification remains a significant challenge for the contemporary interventional cardiologist. We aim to describe the use of intravascular lithotripsy (IVL) in a range of real‐world settings. Methods A retrospective two‐center analysis of patients treated with IVL between June 2018 and November 2019. Technical and procedural success, as well as procedural complications and 30‐day outcomes (death, myocardial infarction, or repeat target vessel revascularization), was recorded. Results Sixty‐five patients underwent IVL: 80% were male and the mean age was 70.1 ± 12.0 years. 54% of patients presented with acute coronary syndrome (ACS) and 68% of patients had intracoronary imaging. Twelve patients required IVL within pre‐existing stents, and 12 underwent IVL in the left main stem. All balloons were successfully delivered with 98.5% procedural success. There was a significant gain in MLA post PCI of 261.9 ± 100% following IVL. There were two procedural complications. At 30‐day follow‐up, there was one death, and one patient required a repeat procedure due to stent underexpansion. Conclusions In this largest real‐world series of imaging‐guided IVL for calcified lesions to date, we demonstrate that IVL is deliverable, safe, and effective at calcium modification especially when intracoronary imaging is used.

lesion adequately through calcium modification. Traditionally, this was attempted with aggressive balloon dilatation with noncompliant balloon and/or modified balloons such as cutting or scoring balloons. However, these balloons are bulky, difficult to deliver, and have higher rate of complications, including coronary perforation. 2 Other calcium modification techniques include rotational atherectomy, orbital atherectomy, and excimer Laser, but they are highly technical with a steep learning curve and require specialized equipment and training for the team, limiting their use and availability. 2 Intravascular lithotripsy (IVL) (Shockwave Medical, Inc, Santa Clara, CA) is a recently approved device for the treatment of calcific coronary lesions. It is evolved from the extracorporeal lithotripsy that has been successfully utilized to treat renal stones since the 1980s. 3 The balloon has two emitters that vaporize the saline/contrast solution when expanded, creating bubbles that expand and collapse within the balloon generating bursts of sonic pressure waves. The pressure waves propagate through the coronary tissue and selectively fractures intimal and medial calcium with an effective pressure of 50 atm, while minimizing trauma to the vessel wall. 4,5 The apposition of the balloon to the vessel wall is essential to facilitate efficient energy transfer and maximize calcium fracture.
The disrupt-CAD study demonstrated the effectiveness of the device in fracturing the calcium, achieving significant luminal gain and stent expansion without the complications commonly associated with atherectomy, such as slow-flow and perforation. 4 Furthermore, IVL calcium modification improved with severity of calcification on imaging, with the greatest effect in the highest tertile suggesting a role of intracoronary imaging in lesion selection. 4 More recently, IVL has also been utilized to optimize underexpanded stents in heavily calcified vessels, in patients presenting with in-stent restenosis (ISR). Case reports suggest that IVL may be a useful technology in this setting. 6,7 IVL also has the advantage of short learning curve as it is still essentially a coronary balloon which is familiar to all interventional cardiologists.
However, real-world data are still limited, and the only case series published to date included only 26 patients and did not utilize any intracoronary imaging. 8 In this article, we present our experience of imaging-guided IVL in contemporary real-world patients.

| METHODS
In this retrospective analysis, consecutive patients treated with IVL at two high volume centers (the Freeman Hospital, Newcastle Upon Tyne, and Royal Stoke University Hospital, UK) between June 2018 and November 2019 were included. The research was carried out in accordance with the Helsinki Declaration (2013), and patients agreed to their records being used to audit the quality and outcomes of their clinical treatment as part of the written consent for the procedure.
Ethical approval was granted by the hospital trusts for audit of outcomes of clinical treatment. There were no specific funding resources for this study.
Following coronary angiography, a decision was made at the discretion of the treating interventional cardiologist to perform percutaneous coronary intervention (PCI) with adjunctive IVL. Although intravascular imaging was not prespecified as an inclusion criterion, in the majority of cases, the target lesion was imaged pre and post PCI by optical coherence tomography (OCT), optical frequency domain imaging (OFDI), or intravascular ultrasound (IVUS), with the choice of imaging modality again at the discretion of the operator.
Baseline demographics and procedural details were collected retrospectively from electronic patient databases. Angiographic calcification was defined as mild (faint radio-opacities noted during cardiac motion before contrast injection), moderate (dense radio-opacities noted before contrast injection), or severe (dense radio-opacitiesnoted before contrast injection comprising both sides of the arterial lumen). 9 Technical success was defined as successful delivery and deploy- OCT images were obtained using a 2.7F Dragonfly OPTIS catheter (Abbott, USA) connected to the Ilumien PCI Optimization System, in accordance with the protocol from the disrupt-CAD imaging sub-study. 5 Prior to image acquisition, a short flush of iso-osmolar contrast was administered to ensure the guide catheter was well engaged with the coronary artery, and the catheter was clear of blood.
The system was calibrated, and the pullback was initiated with a contrast flush (10 mL in the right coronary artery and 15 mL in the left coronary artery). OCT images were obtained in 54 mm segments at a pullback rate of 20 mm/s. OFDI imaging was performed using a FastView imaging catheter (Terumo Corp., Japan) connected to a mobile LUNAWAVE imaging system. Following contrast administration in a similar fashion to OCT imaging, the OFDI catheter is pulled back on an automated pullback motor over a longitudinal distance of up to 150 mm at a rate of 20 mm/s. 11 IVUS images were obtained using the 3.0F 40MHz Opticross imaging catheter (Boston Scientific, USA) connected to the mobile POLARIS multimodality guidance system. Image acquisition was performed at a pullback speed of 1 mm/s using the automated MDU5 motor drive unit.  Table 2 demonstrates the procedure-related details. All balloons were successfully delivered to the lesion, and 53 patients underwent IVL to de novo coronary lesions, with 12 requiring IVL within preexisting stents. One patient received IVL in both the left anterior descending (LAD) and circumflex arteries. There was a heavy burden of calcification when measured by angiography alone, and the majority of patients underwent intracoronary imaging both pre and post PCI, with three patients undergoing both OCT and IVUS imaging. One IVL balloon burst during inflation due to heavy calcification of the lesion.

| RESULTS
In the sub-group of 44 patients with invasive intracoronary imaging (Table 3)  the MSA post PCI, demonstrating the efficacy of IVL, although patients with ISR had a smaller MSA post PCI than those with de novo lesions requiring IVL. Figure 1 exemplifies the calcium fracturing seen on all three imaging modalities.  13 Utilizing intracoronary imaging, our results establish the efficacy of IVL in treating highly calcified coronary lesions in a range of real-world patients (Figure 2 A previous case series highlighted the capacity of IVL to precipitate ventricular ectopics, "shocktopics," and asynchronous cardiac pacing, 15 and there was one patient in our cohort who had VF during IVL delivery and was successfully shocked back to sinus rhythm with no sequelae. The patient who died as a consequence of a distal wire perforation was a high-risk patient with complex calcified coronary disease and left ventricular dysfunction and is a cogent reminder that coronary calcification is an independent predictor of major bleeding events. 16 T A B L E 4 Angiographic and 30-day outcomes Technical success 98.5 Procedural success 86.4 Angiographic complications: • Dissection 0 • Slow flow 0 • Perforation 1.5 • Abrupt closure 0 • No reflow 0 30-d complications: • Death 1.5 • Myocardial infarction 0 • Repeat target vessel revascularization 1.

CONFLICT OF INTEREST
None of the authors has any conflicts of interest to disclose. Javed Ahmed had full access to all of the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis.

TRANSPARENCY STATEMENT
Javed Ahmed affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.