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Taking the rough with the smooth when approaching coronary calcification; should all roads lead to intravascular lithotripsy with provisional rotational atherectomy as the default strategy?
Dr Paul Brady MD, ST7 Interventional Cardiology Trainee, Bristol Heart Institute
Key learning points
Introduction
Coronary calcification is present in 30% of patients presenting with acute coronary syndrome (ACS). (1) As well as increasing difficulty in delivering stents and equipment to the coronary artery during percutaneous coronary intervention (PCI), coronary calcification is also associated with a higher risk of stent thrombosis and ischemic target lesion revascularization at one year. (1, 2) This is primarily because coronary calcification can lead to stent under expansion and have an unfavourable impact on the minimum stent area achieved during PCI, which is an important predictor of stent failure. (3, 4) Fortunately, there is now a wide spectrum of tools designed to attenuate this risk by enhancing the ability of the interventional cardiologist to modify coronary calcification prior to stent deployment and thereby facilitate optimal stent expansion. (5) This includes non-compliant balloons, ultrahigh pressure non-compliant balloons, cutting balloons, scoring balloons, rotational atherectomy, orbital atherectomy, laser atherectomy, and intravascular lithotripsy. This review will focus on just two of these calcium modification strategies; namely rotational atherectomy and intravascular lithotripsy. Based on the relative merits of both these calcium modification strategies and notwithstanding cost, this review explores why the application of intravascular lithotripsy and/or rotational atherectomy can facilitate successful calcium modification across the entire spectrum of calcium morphology and procedural complexity. (6, 7)
Approaching coronary calcification
Coronary calcification can have a heterogenous morphology in the coronary arteries with common patterns including concentric calcification (>270° arch), eccentric calcification (<270° arch), and nodular calcification. (8) Nodular calcification is associated with the highest risk of major adverse cardiac events (MACE), being associated with ACS in particular, accounting for 7.9% of ACS cases. (9, 10)
While angiography has a relatively low sensitivity for detecting coronary calcification, angiographically invisible calcium, i.e. calcification only detectable by intra-coronary imaging, does not appear to inhibit stent expansion and is arguably therefore of less importance in this context. (11) Both optical coherence tomography (OCT) and intravascular ultrasound (IVUS) may however be useful in identifying lesions that may benefit from plaque modification. In one such OCT-based calcium scoring system, lesions with a score of ≥4 (calcium deposit with maximum angle >180 [score 2], maximum thickness >0.5 mm [score 1], and length >5 mm [score 1]) are at risk of stent under-expansion. As such, calcium modification should be considered to treat such lesions. (8) Similarly, an IVUS calcium score that included length i.e. superficial calcium >270° that is ≥5mm in length [1 point], presence of superficial circumferential calcium with a 360° arch [1 point], presence of a calcified nodule [1 point], and small vessel size <3.5 mm [1 point] predicted stent under-expansion. If this score is ≥2, calcium modification should be considered. (12)
Once it has been determined that calcium modification is indicated, intracoronary imaging is essential to understand calcium morphology and ultimately help facilitate an optimal minimum stent area and reduce the risk of future stent failure. (3, 4) Indeed, data from randomised control trials has reinforced the utility of intra-coronary imaging not just in complex PCI, but in all-comer patients. In particular, data from the ULTIMATE trial has shown that IVUS-guided drug eluting stent implantation is associated with significantly lower rates of target vessel failure and stent thrombosis up to 3 years. (13)
Intravascular lithotripsy
This technology uses an angioplasty balloon that generates bursts of sonic pressure waves that selectively fracture calcium in the vessel wall. This results in fractures in both superficial and deep calcium and is equivalent to approximately 50 atmospheres. (14) Intravascular lithotripsy has two major advantages. It uses a coronary balloon-based approach that resembles standard angioplasty, meaning that it is easy to use. In addition, the impact of barotrauma on the vessel is low (balloons expanded to 4 atmospheres to allow contact with the vessel wall and facilitate energy transfer) meaning that intravascular lithotripsy has an excellent safety profile. (15)
The effectiveness of the device was demonstrated by the Disrupt-CAD study which works by fracturing calcium, thereby achieving significant luminal gain and stent expansion with an excellent safety profile. (14) The Disrupt CAD programme consists of four trials (Disrupt CAD I-IV). In Disrupt-CAD I and II OCT sub-studies, it was demonstrated that intravascular lithotripsy can induce multiple circumferential fractures. Interestingly, calcium fracture was observed on OCT in 67% of lesions post intravascular lithotripsy. However, there was no difference in the final minimum stent area in those of who had calcium fractures compared to those who had no calcium fractures, suggesting that all fractures may not be visible on OCT imaging. (14)
The Disrupt CAD III study was a prospective, multicentre, single-arm study carried out in the United States, the United Kingdom, Germany and France. Patients included had heavily calcified de novo coronary lesions with reference vessel diameter 2.5-4.0mm, stenosis >50%, lesion length <40mm or calcium arch of >270 degrees on intra-vascular imaging. A total of 483 patients were evaluated by intention to treat with 100 patients included in the OCT sub-study. Uniquely, the Disrupt CAD III OCT sub-study used OCT imaging pre-procedure, immediately post-treatment and post-stent delivery. Intravascular lithotripsy had an excellent safety profile and was associated with a low rate of angiographic complications, i.e. 0.3% for major dissection, 0.3% for perforation, 0.3% for abrupt closure and 0% for slow flow/no reflow at the end of the procedure. The primary safety endpoint was met with 92.2% of patients being free from MACE at 30 days (cardiovascular death 0.5%, myocardial infarction 7.3%, or target vessel revascularization 1.6%). The primary efficacy endpoint at 30 days was achieved in 92.4% of patients. This was defined as successful stent delivery (99%), residual stenosis <50% (100%), and the absence of in-hospital MACE (93%). (6)
The effectiveness and safety of intravascular lithotripsy in eccentric calcified coronary lesions has been studied using a patient-level pooled analysis from the DISRUPT CAD I and II studies. Data from 47 patients with eccentric lesions, which was defined as having one of its luminal edges in the outer quarter of the apparently normal vessel lumen, were compared to 133 patients with concentric lesions. A similar level of clinical success was achieved with intravascular lithotripsy in both the eccentric lesions and concentric lesions, defined as residual stenosis <50% after stenting with no in-hospital major adverse cardiac events (MACE), (93.6% vs. 93.2%, p=1). (16) Importantly, patient-level pooled analysis from the Disrupt CAD OCT sub-studies also indicates that following treatment with intravascular lithotripsy, there is no differences in acute gain, minimal stent area, or stent expansion in those lesions with a calcified nodule compared to lesions without a calcified nodule. (17) This is important as nodular calcification is traditionally perceived as the most difficult form of calcification to treat and was traditionally an indication for rotational atherectomy to facilitate calcium debulking. (18) However, these results indicate that intravascular lithotripsy can be used to treat nodular calcification via calcium fracture, thereby enabling this modality to be used throughout the full spectrum of coronary calcification.
Rotational atherectomy
Rotational atherectomy is a debulking device that was first introduced in the late 1980s and has the ability to differentially ablate calcified and fibrotic plaques. (19) However, while the introduction of the RotaPro system (Boston Scientific) has made this technology more user-friendly, acquiring skills and confidence in the use of rotational atherectomy is associated with a steep learning curve when compared to balloon-based therapies. In addition, rotational atherectomy is associated with a relatively high risk of major complications. (19) These factors are reflected in UK practise with rotational atherectomy only being used in approximately 2% of cases. (20, 21)
The ROTAXUS study compared the routine use of rotational atherectomy in complex calcified native coronary lesions prior to stenting (n=120) to stenting without rotational atherectomy (n=120). Rotational atherectomy was associated with higher strategy success immediately post PCI (92.5% vs. 83.3%, p = 0.03). (22) Unfortunately, this initial upfront gain was counterbalanced by higher in-stent late lumen loss in the rotational atherectomy group. This was defined as the difference between the immediate post-procedure in-stent minimal lumen diameter and the in-stent minimal lumen diameter at 9-month follow-up angiography (0.44mm ± 0.58mm for rotational atherectomy vs. 0.31mm ± 0.52mm for stenting without rotational atherectomy, p = 0.04). Reassuringly however, there was no difference in MACE at 9 months. This study therefore promoted the use of balloon dilatation with only provisional rotational atherectomy as the default strategy for complex calcified lesions before drug eluting stent implantation.
The more contemporary PREPARE-CALC trial compared rotational atherectomy with modified balloons (cutting or scoring balloons) with 100 patients in each arm. (7) Target vessels were 2.25-4.0mm with severe angiographic calcification and the outcome was strategy success defined as TIMI 3 flow and <20% residual stenosis. Like the ROTAXUS study, in-stent late lumen loss at 9-month angiography was included as an endpoint. The rotational atherectomy arm had better strategy success compared to the modified balloon group (98% versus 81% respectively). This was predominately due to failure to cross associated with modified balloons. There was however a numerically higher, but a non-statistically significant higher rate of procedure-associated complications observed with rotational atherectomy. For example, the risk of perforation, pericardial effusion and slow flow/no flow was 4%, 8% and 2% for rotational atherectomy compared to just 2%, 0% and 0% for modified balloons respectively. Importantly, however, there was no difference in clinical outcomes of death, myocardial infarction or target vessel revascularization at 9 months in both arms. Also, reassuringly, unlike the ROTAXUS study, there was no increase in late in-stent late lumen loss at 9-months follow-up, therefore indicating that rotational atherectomy does not disproportionately stimulate neointima formation and causes more late lumen loss (0.16mm+/-0.39mm for modified balloons versus 0.22mm+/-0.40mm for rotational atherectomy).
While there is a relative paucity in data confirming a clear benefit in the efficacy of rotational atherectomy compared to pre-dilation with standard and modified balloons, it remains an important bail-out device for balloon uncrossable or balloon undilatable coronary lesions. (23)
Conclusion
Intravascular lithotripsy and rotational atherectomy are both very effective at modifying calcification, thereby enabling better stent delivery and stent expansion. Rotational atherectomy use in the UK is low and this may fall further with the routine use of intravascular lithotripsy. The two major benefits of intravascular lithotripsy are its ease of use and excellent safety profile. On this basis, using intravascular lithotripsy as a first-line modality for calcium modification would seem reasonable. The major disadvantage of intravascular lithotripsy is that it may not be deliverable in balloon uncrossable lesions. Having a second-line calcium modification modality is therefore essential. In this regard, the major advantage of rotational atherectomy is that it can be used for balloon uncrossable or undilatable lesions. Furthermore, it can be argued that interventional cardiologists should have a low threshold to switch to rotational atherectomy in this situation. This is because acquiring skills and confidence in the use of rotational atherectomy is associated with a steep learning curve. While rotational atherectomy has a less favourable safety profile compared to other calcium modification modalities, it is likely that more liberal use of this technology, when indicated, may enhance skills and confidence and thereby ultimately help to reduce the risk of adverse events. These two technologies are therefore complementary, with intravascular lithotripsy ideally being a better first choice calcium modification modality and rotational atherectomy being reserved for balloon uncrossable lesions.
References