Coronary lithotripsy: a novel approach to intra-coronary calcification with ‘cracking’ results?

This article is available as a BJC Learning CPD activity

Coronary lithotripsy is a novel approach to percutaneous coronary intervention (PCI). It is based on well-established technology dating back to 1980 when lithotripsy was first used to treat renal calculi. Its application in cardiovascular medicine is a more recent development that involves using a low-pressure lithotripsy balloon to deliver unfocused acoustic pulse waves in a circumferential mechanical energy distribution. This causes fracturing of calcification within the surrounding vasculature, facilitating optimal stent deployment.

This article aims to review recent clinical experience and the published data regarding intravascular lithotripsy (IVL). All relevant articles were identified via PubMed using keywords including “intravascular lithotripsy”, “shockwave” and “coronary”. All studies that contained published datasets regarding IVL with patient numbers >50 were included for review. There were 116 results found. After reviewing all the publications, articles were then tabulated and 17 were found to be relevant, including only four clinical studies.

In this review we found that intracoronary lithotripsy for heavily calcified arteries appears to be a safe, effective, easy-to-use method of dealing with an otherwise technically-challenging and high-risk scenario. It appears to carry low risk, uses low pressures, and exerts its effects on both superficial and deep intravascular calcium. Further prospective data with long-term follow-up will be required to explore both the off-label uses of IVL (such as post-stent dilatation), and the long-term patency of these vessels.

Introduction

The evolution of modern percutaneous coronary intervention (PCI), with miniaturisation of technology, improved device delivery and ancillary devices available to facilitate completion of complex cases, has opened the doors of the catheterisation laboratory to both elderly patients with complex coronary anatomy, as well as those with multiple comorbidities that might have otherwise historically been considered unfit for coronary intervention. As a direct result of this, cardiologists are increasingly treating highly calcified, severely obstructed and chronically occluded coronary vessels.¹ Highly calcified vessels are considerably more difficult to treat, as calcification impedes wire crossing, delaminates drugs and polymers from stents, alters elution kinetics and drug delivery, and impedes stent delivery.² The risk of dissection and increased morbidity is higher in treating calcified vessels, and they account for at least 10% of cases presenting for coronary intervention.³

Diabetic patients present a particular challenge for interventional cardiologists who must deal with more severe calcification, versus non-diabetic patients, while ensuring that an excellent technical result is achieved considering that diabetics are more likely to suffer adverse events including re-stenosis, particularly following a suboptimal revascularisation procedure.⁴

There are many techniques currently available to tackle highly calcified vessels, including high-pressure non-compliant (NC) balloon dilation, double-layer high-pressure balloons, cutting balloons, which purposefully introduce a micro-dissection plane into coronary lesions, and high-speed rotational atherectomy, which involves application of a diamond-tipped metal burr rotating on a wire at 180,000 revolutions per minute, essentially vaporising calcified plaque. Orbital atherectomy has shown some promising results, in diabetics in particular, though similar to rotational atherectomy, it involves high speed rotation of a diamond tipped ‘crown’ that applies contact with 360 degrees of the vessel wall and again rotates at high speed, essentially vaporising calcific plaque.⁵ Each of these devices have their individual strengths and weaknesses (table 1), the most concerning of which is the occasional threat to vessel wall integrity by application of extremely high pressures or mechanical force in order to modify plaque.¹

In terms of under-expanded stents, laser atherectomy has been used effectively, though it is not the treatment of choice in cases of severe calcification.² Rotational and orbital atherectomy are excellent at facilitating lesion crossing, but they may selectively ablate calcified portions of the artery resulting from guidewire bias, meaning that much of the heavy calcification may be left unchanged and there is a significant risk of coronary dissection and perforation when there is a large amount of tortuosity present, as is often the case in calcified lesions.² Atherectomy also has a much higher rate of peri-procedural complications than balloon-based techniques, including slow-flow, myocardial infarction, perforation and major dissection,^2,4,6 though actual rates of significant myocardial infarction appear to be low in experienced centres.⁷ Inadequate stent optimisation is associated with an increased chance of peri-procedural complications occurring, and, in particular, under-expanded stents expose the patient to the risk of stent thrombosis.¹

Originally used to treat renal calculi since 1980,¹ the application of lithotripsy to endovascular medicine refers to the method of applying a low-pressure lithotripsy balloon, typically deployed at six atmospheres, which then emits unfocused acoustic pulse waves delivered in a circumferential uniform mechanical energy distribution,^1,6 with resultant vibration and fracturing of intravascular calcification. Unlike other PCI adjuvants (e.g. cutting balloon), it does not solely depend on mechanical tissue injury induced by physical contact.³ It affects both superficial and deep calcium, resulting in plaque disruption.³ Designed for single use, the balloon catheter is sterile and holds a series of unfocused, electro-hydraulic lithotripsy emitters.¹ A cable connects the balloon catheter to a high-voltage generator which is pre-programmed to deliver a discrete dosage (i.e. pulse) per treatment.

Balloons are available in a variety of diameters (2.5–4 mm) but are currently only available in 12 mm lengths.² The required size is determined by using a 1:1 reference artery ratio. The balloon catheter is then inflated to low pressure (four to six atmospheres), with 10 pulses of sonic energy delivered over 10 seconds per balloon. Next, the balloon is further inflated (to referred vessel size based on a chart provided). This procedure is repeated to deliver at least 20 pulses to each target lesion, with intermittent deflation to facilitate perfusion distal to the target. Each catheter has the capacity to emit up to 80 pulses, with the maximum rate being one pulse per second. If the lesion is distal to the catheter length (i.e. >12 mm), the balloon can be repositioned before repeating the procedure. The acoustic energy is transmitted to the targeted calcified lesion, and causes spall fracture, shear stress, superfocusing, squeezing, cavitation and fatigue.⁹

IVL has been reported as an easy-to-use, efficient and safe approach to achieve plaque modification in severe coronary artery calcification.⁶ It was granted its Conformité Européene (CE) mark in May 2017, following the publication of early results of the Disrupt CAD I (Disrupt Coronary Artery Disease) trial. The concept of lithoplasty as a viable intervention was explored in the Disrupt CAD I and Disrupt CAD II trials.¹ The Disrupt III trial is ongoing.

Materials and method

We conducted a PubMed search using the keywords “Intravascular lithotripsy”, “Shockwave” and “Coronary”. There were 116 results found. Articles that examined extracorporeal or extracardiac lithotripsy were excluded. After reviewing all the provided publications, articles describing clinical studies with patient numbers >50 were included: 17 were found to be relevant, including eight case reports, four completed studies, and five review articles.

Clinical trials

Disrupt CAD I trial

This was a multi-centre, prospective, single-arm study of IVL prior to stent implantation. The interventional study recruited 60 participants across seven sites, and used the Shockwave Coronary Lithoplasty® System to pre-dilate calcified stenosed coronary arteries.³ Using optical coherence tomography (OCT), the trial showed improved circumferential calcium fracture and luminal gain,¹⁰ with 98.3% device success (being defined as correct device delivery and application of lithotripsy to the target lesion) and 100% stent delivery. Vascular complications were minimal post-procedure, with a 30-day major adverse cardiac event (MACE) rate of 5% – these included target vessel revascularisation, myocardial infarction (MI) or cardiac death.¹

Disrupt CAD II trial

This was a multi-centre, prospective single-arm study conducted at 15 hospitals across nine countries, which looked at the safety and effectiveness of intracoronary lithotripsy.² Over the course of 10 months (May 2018 to March 2019), 120 patients were enrolled in the study. Participants were included if they demonstrated a single target lesion requiring PCI with a stenosis diameter ≥50%, and lesion length ≤32 mm in native coronary arteries. There were 94.2% of participants found to have severe coronary artery calcification, defined as calcification within the lesion on both sides of the vessel assessed by angiography.² Coronary lithotripsy was successfully applied to all cases.

Using OCT, independent labs examined the mechanism of action and intraluminal effects of lithotripsy. No abrupt closure, slow flow, no-reflow, major dissections or perforations occurred. Calcium fracture was identifiable on invasive imaging in 78.7% of lesions. The primary end point was in-hospital major adverse cardiac events (MACE) including cardiac death, MI, or target vessel revascularisation. These only occurred in 5.8% of patients. They found that coronary lithotripsy was safely performed with high procedural success (92.4%). The Disrupt III trial is currently underway. It is a single-arm study and aims to enrol 400 patients from 50 centres across Europe and the USA.¹

TCT-653 Intravascular Lithotripsy for Lesion Preparation trial

This prospective study¹⁰ sought to determine the strategy success and safety of intravascular coronary lithotripsy on calcified lesions in a wide cohort of patients. Patients with moderately and severely calcified coronary lesions on invasive imaging were screened at three centres in Spain and Germany starting in April 2018. Patients were assigned to three groups: group A, primary IVL therapy for patients with circumferential calcified de novo coronary lesions; group B, secondary IVL therapy for patients with moderately or severely calcified coronary lesions in whom conventional non-compliant balloon dilatation failed; and group C, tertiary IVL therapy in patients with in-stent stenosis due to stent under-expansion after previous stenting.

Through February 2019, 71 patients with 78 lesions were eligible for IVL. The mean diameter of calcified stenosis on quantitative coronary angiography was 72.0% (± 13.8%) at baseline and decreased to 17.7% (± 15.84%), p<0.01, after IVL, with an acute gain of 1.9 mm (± 0.63 mm). Mean minimal luminal diameter was 1.0 ± 0.5 mm at baseline and increased after IVL to 2.9 (± 0.6) mm. The primary end point (defined as procedural success and safety) was reached in 57 participants (73%). Four type B dissections (three in group A, one in group B) were observed without further sequelae. There were no in-hospital MACE. In one patient (1.6%), target lesion failure was observed on routine follow-up coronary angiography, and the patient required revascularisation. According to the subgroups, strategy success in the primary IVL treatment (group A) and secondary IVL treatment (group B) was reached in 81.3% and 83.3% of cases, respectively. In tertiary IVL therapy (group C), the primary study end point was reached in 64.7% of cases. Device delivery and IVL treatment was performed in all lesions without complication. Seven IVL balloons ruptured during treatment, without any sequelae. Rupture was observed in most cases after repositioning of the balloon within the calcified lesion.

Extending Application of Intravascular Lithotripsy to a High-Risk Real-World Population trial

Yeoh et al. conducted this interventional study at King’s College Hospital, London, looking at IVL for PCI in severely calcified coronary vessels.¹¹ There were 54 participants enrolled. Inclusion criteria included an undilatable lesion, severe calcification on angiography, or on intravascular imaging. OCT was used to review outcomes. Total procedural success was found to be 91%, with 100% of cases having successful stent delivery. No cases of coronary perforation, no-reflow or target lesion failure occurred.

Indications

The Shockwave C2 Coronary IVL System is indicated for lithotripsy-enhanced, low-pressure balloon dilatation of calcified, stenotic de novo coronary arteries prior to stenting (i.e. vessel preparation). This device is not intended to be used for stent delivery or in carotid or cerebrovascular arteries.

Invasive imaging

IVL is designed to modify calcific lesions. It has been suggested by some authors that invasive imaging to define plaque composition should always be performed in advance of considering IVL, as the location of calcific intra-arterial densities is not always readily apparent on angiographic projections. Typically, operators should identify a calcific arc of at least 270° before considering IVL as this is the usual arbitrary cut-off used to decide whether rotational atherectomy is indicated. Intra-arterial calcium is easily identified using intravascular ultrasound, though OCT can also be used. In particular, repeat intravascular imaging following IVL allows operators to identify fractures in calcific sheets in order to confirm that successful plaque modification has been achieved. Performing intracoronary imaging ahead of IVL is preferable as operators can also ensure 1:1 balloon sizing versus the reference vessel diameter, which is encouraged by the manufacturer.¹² Ideally, operators should confirm that calcium has been successfully modified before stent deployment, as modification of calcific plaque behind stent struts can be more challenging to achieve, necessitate higher pressure post-dilation, and, in the case of IVL post-stenting, the interaction between the IVL balloon and polymer-coated drug-eluting stents is unknown, to date.

Discussion

IVL is a novel technique in the cardiac catheterisation laboratory, given that the Shockwave Medical^TM system has only recently become commercially available. It has been incorporated into recent treatment algorithms,¹ and we suggest consideration of individual patient anatomy when making decisions regarding IVL versus rotational atherectomy, including: presence of a major side branch, tortuosity, lesion length, presence of a pre-existing stent and difficulty in balloon delivery.

A less publicised off-label indication use for IVL is in stent optimisation where gross stent under-expansion is present due to concentric calcification. As evidenced by cases we have seen* and other authors,^6,8,13-18 IVL appears to be highly effective for this challenging scenario, which is best avoided by careful lesion preparation, but will nonetheless occasionally be encountered. In IVL, acoustic waves appear to travel through the stent and their harmonic pulse waves are still able to cause sufficient modification of dense vascular calcium to allow full stent expansion. Conversely, rotational atherectomy must obliterate the stent before allowing modification of deep calcium where a stent has already been deployed. As a result, there is always a possibility that the burr of the rotablator may become trapped in the artery beyond the stent – a devastating complication that can require emergency open-heart surgery.¹⁹

In terms of strengths, IVL has been described as easy to use, efficient and safe.⁶ It also does not appear to have any effect on soft tissue, limiting its effects to the calcified lesions within the vessel wall – this minimises the risk of complications such as dissection.¹ No major dissections with negative outcomes have occurred, as far as we are aware, following the use of intracoronary lithotripsy.² The low pressures that are required for lithotripsy (typically four to six atmospheres) make it an attractive modality, particularly where high-pressure post-dilations may be required otherwise, with an associated higher risk of rupture. As calcium is fractured in situ, the risk of distal embolisation appears low (but this is yet to be validated by magnetic resonance imaging [MRI] studies).

There are some notable limitations with IVL. In particular, there are no long-term follow-up data available, and the long-term patency of vessels treated with IVL is unknown.¹⁹ Furthermore, IVL may require extensive vessel preparation with techniques such as rotational atherectomy to allow IVL catheter delivery, and, therefore, the incremental expense associated with these hybrid ‘Rota-Tripsy’ procedures may be considerable.⁶ The effects of IVL on the integrity of drug-eluting stents including the abluminal polymer-drug/endothelial interface is unknown and unstudied to date.

Conclusion

In summary, IVL for heavily calcified arteries appears to be a safe, effective, easy-to-use method of dealing with an otherwise technically-challenging, frequently encountered and high-risk scenario. It appears to carry low risk, acceptable cost versus conventional alternative methods, uses low pressures, and exerts its effects on both superficial and deep calcifications. However, the lack of long-term follow-up data mandates further study before widespread adoption.

Key messages

• Intravascular lithotripsy (IVL) appears to be a safe, effective, user-friendly method of dealing with heavily calcified arteries in an otherwise technically challenging and high-risk scenario
• IVL carries a low risk, uses low pressures, exerts its effects on both superficial and deep calcium deposits
• Off-label application of IVL for post-stent dilatation should be considered when there is ineffective post-dilation with conventional non-compliant balloons post-stenting in the setting of circumferential calcification
• Further data are required to explore both the off-label uses of IVL (such as post-stent dilatation), and the long-term patency of these vessels due to the unknown interaction between the IVL catheter and the polymer/drug coating of drug-eluting stents

Conflicts of interest

None declared.

Funding

None.

Editors’ note

*The authors will write about the use of IVL in individual patients in our next issue.

This article is available as a BJC Learning CPD activity

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