Lesion Preparation for Severely Calcified Coronary Artery Disease　― Intravascular Lithotripsy as a New Option ―

The development of the drug-eluting stent (DES) has significantly improved clinical outcomes for patients with coronary artery disease (CAD).¹ However, severe coronary calcification is a risk factor for initially unsuccessful revascularization, as well as late stent failure.² Therefore, appropriate lesion preparation before DES implantation is of utmost importance for severely calcified coronary lesions. Intravascular lithotripsy (IVL) is a new technology using sonic pressure waves, and several clinical trials in severely calcified CAD have been conducted. The disrupt CAD I was a pre-market European study enrolling 60 patients to show the safety and performance of IVL in heavily calcified coronary lesions,³ and disrupt CAD II was a post-market European registry study enrolling 120 patients.⁴ Disrupt CAD III was a prospective, multicenter, single-arm study enrolling 431 patients to obtain FDA approval for use of coronary IVL in the USA.⁵ These studies showed the safety and effectiveness of coronary IVL, but did not include Japanese patients.

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In this issue of the Journal, Saito et al⁶ report on the disrupt CAD IV study enrolling 64 patients to support regulatory device approval of coronary IVL in Japan. A summary of the disrupt CAD IV study is as follows: (1) freedom from 30-day major adverse cardiac events (MACE) was 93.8%, which was non-inferior compared with the IVL control group (from the disrupt CAD III), (2) procedural success rate was 93.8%, which was also non-inferior compared with the IVL control group, (3) device crossing and angiographic success rates were 98.4% and 98.4%, respectively, and (4) post-IVL calcium fracture occurred in 53.5% of study lesions in optical coherence tomography analysis. The main results were similar to those of the previous disrupt CAD studies, suggesting the safety and effectiveness of coronary IVL for Japanese patients. This study is important for Japanese interventional cardiologists as well as Japanese patients, because coronary IVL is not allowed to be used in Japan. If coronary IVL is approved by the Pharmaceuticals and Medical Devices Agency, it would become a new option for lesion preparation for severely calcified CAD in Japan.

In the contemporary era of percutaneous coronary intervention, we have several lesion preparation devices for coronary calcified lesions (Table). Rotational atherectomy (RA) directly ablates the calcified plaque, and the main target of RA is superficial calcification. Crossing ability of RA is excellent, and if any devices cannot cross the calcified lesion, RA would be the last resort. However, unique complications such as burr entrapment may occur with RA,^7,8 and the operator’s experience is closely associated with the incidence of severe complications.^8,9 Orbital atherectomy (OA) directly ablates the calcified plaque, when the operator moves the device backwards as well as forwards. The manipulation of OA may be easier than with RA, partly because only a single burr size is applicable for OA. However, unique complications such as burr dislodgement may occur with OA.^10,11 Cutting/scoring balloon theoretically can make several cracks in the calcified plaque using cutting/scoring blades. Although the rated burst-pressure is usually lower in cutting/scoring balloons than in conventional non-compliant balloons, the ability to make a crack is considered to be greater with cutting/scoring balloons than with conventional balloons. However, it is difficult for the cutting/scoring balloon to make a crack in a dense sheet of calcification. Unlike conventional non-compliant balloons, some non-compliant balloons have a very-high-rated burst-pressure such as 24 atm. In clinical practice, these very-high-rated burst-pressure balloons might make a crack in a lesion where cutting/scoring balloons failed. However, these types of balloons have a large crossing profile, which results in poor crossability. Coronary IVL may make several cracks in calcified plaque using sonic pressure waves, and may make cracks in deep as well as superficial calcification. There are few comparative data on crossing ability between coronary IVL and other devices. Because its crossing profile is 0.042 (similar to that of thin-strut DES), crossing ability may not be excellent in the coronary IVL. Based on the results of disrupt CAD I, II, III, and IV, the risk of complications is low with coronary IVL. However, if an IVL balloon explodes during lithotripsy, it can generate an uncontrolled dissection or even vessel rupture.¹² Furthermore, an important precaution for use is that coronary IVL should not be used for in-stent lesions. Stent-underexpansion caused by severe calcification is difficult to treat. RA is sometimes used (stent ablation),⁹ but the long-term outcomes of RA for in-stent lesions have not been satisfactory.¹³ Coronary IVL theoretically has potential to treat stent-underexpansion, and several groups have reported successful cases.^14,15 However, the safety of coronary IVL for in-stent lesions has not been verified yet. We should follow the instructions for use, especially with new technologies.

Table. Lesion Preparation Devices for Calcified Coronary Lesions

	Rotational atherectomy	Orbital atherectomy	Cutting/scoring balloon	Non-compliant balloon	Intravascular lithotripsy
Mechanism of action	Directly ablate the calcified plaque. The main target is superficial calcification.	Directly ablate the calcified plaque. Ablate the calcified plaque when operator moves the device backwards as well as forwards.	Make several cracks in calcified plaque using cutting/scoring blades.	Make cracks in the calcified plaque using high pressure.	Make several cracks in calcified plaque using sonic pressure waves. May make cracks in deep calcification as well as superficial calcification.
Crossing ability	Excellent. If any other devices (balloon, microcatheter) cannot cross the lesion, rotational atherectomy is the last resort.	Fair. Crossing ability is better when using GlideAssist mode. However, lesion crossing in GlideAssist mode is off-label.	Fair to good. Depends on each device.	Fair to good. Depends on each device. Balloons with very-high-rated burst-pressure usually have a large crossing profile, which would result in poor crossability.	Not sufficient experience with regard to the comparison of crossing ability with other devices. Crossing profile is 0.042 inches, which is similar to thin- strut drug-eluting stents.
Risk of complications	Unique complications such as burr entrapment may occur.	Unique complications such as device dislodgment may occur.	May be less as compared with compliant balloon dilatation for calcified lesions.	May be less as compared with compliant balloon dilatation for calcified lesions.	If a balloon explodes during lithotripsy, it can generate an uncontrolled dissection or even a vessel rupture.12
Specific training before using the device, and operator’s learning curve	Necessary. Operator’s experience is closely associated with the incidence of complications.8	Necessary. May be easier than rotational atherectomy, partly because only single size burr is applicable for orbital atherectomy.	Does not require specific device training.	Does not require specific device training.	Not determined in Japan. Operators have to learn the mechanism of action before using this device.
Indication for in-stent lesion	Possible	No	Yes	Yes	No
Clinical experience	Clinical experience >20 years in USA, Europe, and Asia.	Rapidly increasing clinical experience in USA and parts of Asia. No CE mark.	Abundant clinical experience.	Abundant clinical experience.	Not sufficient clinical experience.

In summary, IVL is a new option for the treatment of severely calcified coronary lesions, and the disrupt CAD IV study showed high procedural success rates as well as low MACE rates in severely calcified lesions in a Japanese population.⁶ Because each lesion preparation device has different characteristics, interventional cardiologists should select the appropriate one for each case, seeking the balance between safety and efficacy.

Financial / Nonfinancial Disclosures

K.S. has received speaking honoraria from Abbott Vascular, Boston Scientific, Medtronic Cardiovascular, Terumo, OrbusNeich, Japan Lifeline, Kaneka, and NIPRO; he has served as a proctor for Rotablator for Boston Scientific, and has served as a consultant for Abbott Vascular and Boston Scientific.

References

• 1.   Piccolo R, Bonaa KH, Efthimiou O, Varenne O, Baldo A, Urban P, et al. Drug-eluting or bare-metal stents for percutaneous coronary intervention: A systematic review and individual patient data meta-analysis of randomised clinical trials. Lancet 2019; 393: 2503–2510.
• 2.   Mori H, Finn AV, Atkinson JB, Lutter C, Narula J, Virmani R. Calcified nodule: An early and late cause of in-stent failure. JACC Cardiovasc Interv 2016; 9: e125–e126.
• 3.   Brinton TJ, Ali ZA, Hill JM, Meredith IT, Maehara A, Illindala U, et al. Feasibility of shockwave coronary intravascular lithotripsy for the treatment of calcified coronary stenoses. Circulation 2019; 139: 834–836.
• 4.   Ali ZA, Nef H, Escaned J, Werner N, Banning AP, Hill JM, et al. Safety and effectiveness of coronary intravascular lithotripsy for treatment of severely calcified coronary stenoses: The Disrupt CAD II study. Circ Cardiovasc Interv 2019; 12: e008434.
• 5.   Hill JM, Kereiakes DJ, Shlofmitz RA, Klein AJ, Riley RF, Price MJ, et al. Intravascular lithotripsy for treatment of severely calcified coronary artery disease. J Am Coll Cardiol 2020; 76: 2635–2646.
• 6.   Saito S, Yamazaki S, Takahashi A, Namiki A, Kawasaki T, Otsuji S, et al; for the Disrupt CAD IV Investigators. Intravascular lithotripsy for vessel preparation in severely calcified coronary arteries prior to stent placement: Primary outcomes from the Japanese Disrupt CAD IV study. Circ J 2021; 85: 826–833.
• 7.   Sakakura K, Ako J, Momomura S. Successful removal of an entrapped rotablation burr by extracting drive shaft sheath followed by balloon dilatation. Catheter Cardiovasc Interv 2011; 78: 567–570.
• 8.   Sakakura K, Inohara T, Kohsaka S, Amano T, Uemura S, Ishii H, et al. Incidence and determinants of complications in rotational atherectomy. Circ Cardiovasc Interv 2016; 9: e004278.
• 9.   Sakakura K, Ito Y, Shibata Y, Okamura A, Kashima Y, Nakamura S, et al. Clinical expert consensus document on rotational atherectomy from the Japanese Association of Cardiovascular Intervention and Therapeutics. Cardiovasc Interv Ther 2021; 36: 1–18.
• 10.   Otowa K, Chikata A, Maruyama M, Usuda K. Successful retrieval of dislodged classic crown on coronary orbital atherectomy. Cardiovasc Interv Ther, doi:10.1007/s12928-020-00693-z.
• 11.   Yamamoto H, Takaya T, Uzu K, Takahashi Y, Kawai H. Coronary orbital atherectomy at the ostium of an anomalous right coronary artery: A double-edged sword. JACC Cardiovasc Interv 2020; 13: 2937–2939.
• 12.   Lopez-Lluva MT, Jurado-Roman A, Sanchez-Perez I, Abellan-Huerta J, Lozano Ruiz-Poveda F. Shockwave: Useful but potentially dangerous. JACC Cardiovasc Interv 2019; 12: 500–501.
• 13.   Hachinohe D, Kashima Y, Hirata K, Kanno D, Kobayashi K, Kaneko U, et al. Treatment for in-stent restenosis requiring rotational atherectomy. J Interv Cardiol 2018; 31: 747–754.
• 14.   Alawami M, Thirunavukarasu S, Ahmed J, El-Omar M. Intravascular lithotripsy to treat an underexpanded coronary stent: 4-Month angiographic and OCT follow-up. Catheter Cardiovasc Interv 2020; 96: 1251–1257.
• 15.   Yeoh J, Cottens D, Cosgrove C, Mallek K, Strange J, Anderson R, et al. Management of stent underexpansion using intravascular lithotripsy: Defining the utility of a novel device. Catheter Cardiovasc Interv, doi:10.1002/ccd.28715.