Cracking Calcium With the C2+ Lithotripsy Balloon
Can Greater Pulse Availability Translate to Enhanced Procedural Outcome Whilst Maintaining a High Safety Profile?
Can Greater Pulse Availability Translate to Enhanced Procedural Outcome Whilst Maintaining a High Safety Profile?
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Any views and opinions expressed are those of the author(s) and/or participants and do not necessarily reflect the views, policy, or position of Cath Lab Digest or HMP Global, their employees, and affiliates.
Jonathan Hinton, MD1; Gao Ong, MD2; Mae Bethell, MD1; Jennifer Barraclough, MD3; Ganeev Malhotra, MD2; Thomas Johnson, MD3,4; Simon J. Wilson, MD2; James C. Spratt, BSc, MB ChB, MD2; Julian Strange, MD3; Peter O’Kane, MD1
1Dorset Heart Centre, Royal Bournemouth Hospital, Bournemouth
2Intervention and Coronary Artery Disease Group, St Georges University Hospital, London
3Bristol Heart Institute, University Hospital Bristol, Bristol
4University of Bristol, Bristol
United Kingdom
The authors can be contacted via Jonathan Hinton, MD, at jonathan.hinton@uhd.nhs.uk.
Coronary artery calcification is a common challenge in percutaneous coronary intervention (PCI), often leading to stent under-expansion and failure.1-5 Intravascular lithotripsy (IVL) has emerged as a safe and effective tool for calcium modification, with the DISRUPT CAD trials showing favorable outcomes even in complex lesions.6-10 IVL uses acoustic waves to fracture calcium and improve vessel compliance, and its balloon-based delivery system offers a short learning curve and ease of use compared to atherectomy.
While IVL has shown promise in a range of scenarios, including STEMI, eccentric lesions in combination with rotational atherectomy, and stent failure due to calcific under-expansion,12-20 limitations remain, such as balloon crossing profile and the pulse cap of the C2 balloon (80 pulses) (Shockwave Medical). Registry data suggest higher pulse counts may improve outcomes.21 This analysis evaluates patient and procedural characteristics, along with medium-term outcomes, from early experience with the C2+ IVL balloon (Shockwave Medical), which delivers up to 120 pulses.
Method
Study participants and data collection
This is a retrospective analysis of consecutive patients treated with IVL for coronary calcification using the C2+ Shockwave balloon from its implementation in November 2022 through December 2023, with comparison to consecutive patients in the preceding year undergoing C2 Shockwave balloon treatment, taking place across the three hospitals (University Hospital Dorset, University Hospital Bristol & Weston, and St. George’s University Hospital). This analysis received approval from each of the local audit/service evaluation groups. Baseline demographics, comorbidity details, and details of the procedure were taken from the British Cardiovascular Intervention Society database. Target vessel revascularization (TVR) and mortality during the analysis were also recorded.
Procedure
Patients were included in this cohort if the treating interventional cardiologist felt that there was significant calcification requiring modification with IVL. The size of IVL balloon and number of pulses delivered was at the discretion of the supervising interventional cardiologist. IVL was performed using the Shockwave C2 system as per the standard IVL technique using the C2 or C2+ balloon.22
Statistical analysis
Patient demographics and comorbidities are reported per patient, while procedural data are reported per procedure to account for patients who underwent more than one IVL procedure. Continuous variables are shown as medians with interquartile ranges (IQR), and compared between C2 and C2+ groups using the Mann-Whitney U test. Categorical variables are reported as counts and percentages, with group comparisons made using the Chi-squared test.
Target vessel revascularization (TVR) is presented per lesion, and mortality is presented per patient, both analyzed using Kaplan-Meier curves. Given prior data linking higher pulse counts with lower TVR, TVR was also analyzed per procedure by grouping total IVL pulses into ≤80 pulses, 81-120 pulses, and >120 pulses as categories. Additional TVR comparisons were made by sex and use of intracoronary imaging.
Kaplan-Meier analyses were also used to compare TVR in the entire cohort across several subgroups: acute coronary syndrome (ACS) versus chronic coronary syndrome (CCS, also known as stable ischemic heart disease), ST-elevation myocardial infarction (STEMI) versus non STEMI, IVL with versus without adjunctive atherectomy or cutting balloon, and treatment of in-stent restenosis versus de novo lesions. Log-rank tests were used for all group comparisons. Analyses were conducted using SPSS v29.0 (IBM Corp).
Results
Patients
A total of 264 patients were treated with the C2+ IVL balloon, accounting for 274 procedures, while 286 patients received the C2 balloon in the preceding year, totaling 296 procedures. The median age of the overall cohort was 74 years (interquartile range [IQR] 65-80), and 22.7% were female. Baseline characteristics were generally well-matched between groups, with the only significant difference being a higher median creatinine level in the C2+ group (90 µmol/L versus 85 µmol/L, P=.004). Full demographic and comorbidity data are summarized in Table 1.
Presentation and procedures (Table 2)
There was a balanced distribution of ACS and CCS presentations, with no significant difference between the C2 and C2+ cohorts. IVL was used in previously stented segments in 8.8% of cases, again with similar rates between groups. Left main PCI was more frequent in the C2+ cohort (20.4% versus 12.8%, P=.015), and use of adjunctive devices such as rotational atherectomy (13.5% versus 3.4%, P<.001) and cutting balloons (34.3% versus 26.4%, P=.039) was also higher in the C2+ group.
Intravascular imaging was widely used (86.3% overall), with no significant difference between groups. The C2+ cohort had significantly higher total IVL pulse counts than the C2 cohort (median 120 versus 80 pulses, P<.001), reflecting the C2+ balloon’s expanded capacity. Although most cases used a single IVL balloon, larger balloon sizes were more frequently used in the C2+ group. There was also a non-significant trend toward longer stent lengths in the C2+ cohort.
Procedural and follow-up outcomes
In terms of vessel perforation (as opposed to distal wire perforation), there were three (1.0%) perforations in the C2 cohort and three (1.1%) perforations in the C2+ cohort. In the entire cohort, at a median follow-up of 324 days, there were 76 deaths. Median follow-up in C2+ cohort was 172 days (IQR 101-264 days) and median follow up in C2 cohort was 752 days (IQR 643-859 days), with 54 deaths in C2 cohort and 22 deaths in the C2+ cohort. There was no difference in mortality between the C2 and C2+ cohorts on Kaplan-Meier curve and log rank analysis (Figure 1). There was a significant increase in the frequency of TVR with the use of the C2+ when comparing the C2 and C2+ cohorts, but the split in the curves occurred after around 200 days (Figure 2). When the two cohorts were combined, those patients with ≤80 pulses had significantly lower TVR when compared with those with 81-120 pulses and >120 pulses (Figure 3).
There was no difference in TVR between sexes (Supplementary Figure 1). There was no difference in TVR when ACS cases were compared with CCS cases (P=.622) and STEMI cases with the remainder of the cohort (Supplementary Figures 2-3) (P=.706). The TVR frequency was significantly higher in patients treated with IVL within a previously stented segment compared with de novo disease (Supplementary Figure 4) (P=.005). Finally, there was no difference in TVR in cases where IVL was used alone versus in conjunction with rotational/orbital atherectomy, cutting balloons, or intracoronary imaging (Supplementary Figure 5).
Discussion
This is the first analysis comparing the C2+ IVL balloon (120 pulses) with the standard C2 (80 pulses). Use of the C2+ was associated with more complex cases, including higher rates of left main PCI and adjunctive atherectomy, and a higher frequency of target vessel revascularization (TVR). This may reflect selection bias, as operators possibly used C2+ in more complex anatomy, supported by longer stent lengths and greater use of imaging. While both cohorts showed good acute outcomes, the difference in TVR became apparent beyond 200 days, and longer follow-up is warranted.
Compared with the DISRUPT CAD III and IV trials, which enrolled shorter, more focal lesions (≤40 mm),8-10 our study population presented with more complex disease, evident in the longer stents and broader use of adjunctive tools. Intriguingly, while the FRANCE-LILI registry showed reduced TVR with more pulses,21 our analysis showed the opposite. However, the widespread use of intracoronary imaging in our study likely led to higher pulse counts in more advanced disease, making pulse number a surrogate for lesion complexity rather than an independent predictor of outcome.
IVL showed favorable results in ACS and STEMI patients, with similar TVR rates compared to CCS cases. This is notable given the limited data on plaque modification in STEMI due to concerns around embolization with atherectomy.8,9,15,20,23 IVL may provide an accessible, safe alternative in this setting, especially for operators without atherectomy experience.
Despite more pulses with the C2+, operators used more adjunctive tools, suggesting evolving practice toward hybrid strategies such as “rotashock.” While promising, evidence supporting the added benefit of multimodality plaque modification, especially involving IVL, remains limited.24-27
We also observed frequent IVL use for stent under-expansion. Although this subgroup had higher TVR, as expected for restenosis cases, the one-year TVR rate (22.2%) was in line with other cohorts.12,18,20,28-31 These findings support the real-world safety and utility of IVL in previously stented segments.
Lastly, the perforation rate in this analysis was slightly higher (1.0% with C2 and 1.1% with C2+) compared with the Disrupt CAD III and IV trials, which reported perforation rates of 0.3% and 0.0%, respectively.8,9 This difference is likely attributable to the more complex lesions and use of larger balloons in our study, rather than any specific safety concern with the C2+ device.
Limitations
This analysis has several limitations. First, although data were collected from three sites, all were early adopters of the C2+ balloon with established calcium modification programs, limiting generalizability, especially in settings with low use of intracoronary imaging. Second, this was a retrospective analysis based on data from the British Cardiovascular Intervention Society database, which lacks formal adjudication. Additionally, TVR events may be underreported if patients sought care outside the contributing institutions. Lastly, the C2+ cohort had a median follow-up of only 172 days, reducing the power to assess medium-term outcomes compared to the C2 cohort.
Conclusion
The C2+ IVL balloon’s greater pulse availability has been shown to be as safe as the C2 IVL balloon and similarly, is suitable for a broad range of presentations and calcific lesion subsets. The use of the C2+ IVL balloon is associated with good clinical outcomes in a complex, real-world cohort of patients with severe calcification. However, from this retrospective analysis, efficacy does not appear to correlate with the number of pulses used at a lesion level.
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