Prepared by: Dr. Seda Kurat Güldoğuş, Dr. Kemal Göçer

Name of the study: Randomised Comparison of Lithotripsy vs. Conventional Preparation in Severely Calcified Coronary Lesions (BALI)

Published in: EuroPCR 2025

Introduction
Coronary artery disease (CAD) continues to be a major cause of morbidity and mortality, particularly in elderly patients and those with multiple cardiovascular risk factors. Coronary artery calcification, especially when severe and diffuse, poses a significant challenge to the success of percutaneous coronary interventions (PCI). Calcified lesions hinder plaque modification during stent deployment, resulting in suboptimal stent expansion, increased residual stenosis, and ultimately, target vessel failure. Moreover, compared to fibrotic plaques, calcification is more frequently associated with acute complications such as dissection and slow flow. These challenges expose the limitations of conventional methods used for treating calcified coronary lesions, such as traditional balloon angioplasty, cutting/scoring balloons, and rotational atherectomy. In recent years, intravascular lithotripsy (IVL), a modern adaptation of extracorporeal shockwave lithotripsy for intravascular use, has emerged as a promising technique for mechanically modifying severe calcification. IVL works by delivering low-energy ultrasonic pressure waves that fracture intravascular calcium, aiming to facilitate stent delivery and reduce complication rates. Its ease of clinical use and favorable early results have led to its rapid adoption; however, robust data from randomized controlled trials (RCTs) remain limited. Therefore, multicenter, randomized studies evaluating the clinical efficacy and safety of IVL in comparison with conventional plaque modification techniques are critically needed.

Objective
The primary aim of this study is to evaluate the clinical and angiographic efficacy and safety of IVL in patients with severely calcified coronary artery disease, in comparison with conventional balloon angioplasty and other plaque modification strategies. While existing literature clearly demonstrates that severe coronary calcification adversely affects PCI outcomes and increases procedural risks, the potential role and advantages of IVL in overcoming these challenges remain to be definitively established. This study seeks to provide a comparative perspective on key outcomes such as procedural failure, residual area stenosis, target vessel failure, and complication profiles. Additionally, it aims to reinforce the role of IVL in clinical practice by supplying stronger evidence to inform decision-making in the management of severely calcified coronary lesions.

Methods
This multinational, multicenter, randomized controlled trial enrolled 200 patients with angiographically confirmed severe coronary calcification and documented ischemia. Participants were randomly assigned in a 1:1 ratio to either the IVL group (n=99) or the conventional plaque modification group (e.g., cutting/scoring balloons, rotational atherectomy; n=101). All target lesions were thoroughly evaluated using optical coherence tomography (OCT) prior to PCI. Post-stent deployment and post-dilation, plaque modification was again assessed via OCT. Patients underwent clinical and OCT follow-up at 1 and 2 years post-procedure. Inclusion criteria included severe coronary calcification as defined angiographically by Mintz et al., a diagnosis of stable or unstable coronary syndrome or NSTEMI, and evidence of functional or anatomical ischemia. Patients with STEMI, chronic total occlusions, left ventricular ejection fraction (LVEF) <35%, or advanced renal failure were excluded. The primary endpoint was procedural failure, defined as unsuccessful stent delivery or deployment, residual area stenosis ?20%, and 1-year target vessel failure. Secondary endpoints included myocardial infarction (MI), repeat revascularization, death, and procedural complications.

Results
Baseline demographic and clinical characteristics were similar between groups. Mean age was 75±8 years in the IVL group and 74±7 years in the conventional group. Mean LVEF was comparable (55% vs. 54%). The majority of lesions were located in the left anterior descending (LAD) and right coronary artery (RCA). The rate of procedural failure was 1% (1/99) in the IVL group and 0% in the conventional group. OCT-assessed residual area stenosis ?20% was observed in 32.3% of the IVL group versus 44.6% in the conventional group. Target vessel failure occurred in 4% of patients in the IVL group and in 10.9% of those in the conventional group. Although these differences were not statistically significant, they demonstrated a favorable trend toward IVL. The incidence of myocardial infarction was 0% in the IVL group and 5% in the conventional group. Rates of flow-limiting dissection and vessel perforation were slightly higher in the IVL group but did not reach statistical significance. The post-dilation balloon diameter and stent length were greater in the IVL group, while the balloon inflation pressure was lower. These findings suggest that IVL more effectively modifies calcified plaques, offering technical advantages during stent implantation.

Discussion
This study provides important insights into the clinical efficacy and safety of intravascular lithotripsy in the management of severely calcified coronary lesions. The lower rates of procedural failure and residual stenosis in the IVL group indicate that this technology may offer mechanical advantages in plaque modification. Despite the use of longer stents and larger balloon diameters, the lower inflation pressure needed during post-dilation in the IVL group suggests improved vessel compliance due to more effective calcium fracture. However, a numerically higher incidence of complications such as perforation and dissection underscores the need for cautious application and further investigation into IVL’s safety profile. The observed reduction in target vessel failure with IVL is promising for long-term treatment success. Nevertheless, since the confidence intervals included 1 and the p-values approached the threshold of statistical significance, the results should be interpreted with caution. Overall, the findings support the role of IVL as an effective alternative in the treatment of severely calcified coronary lesions, but highlight the need for further large-scale, long-term RCTs to validate its benefits and assess its risk profile.

Conclusion
Intravascular lithotripsy appears to be a promising technique for improving PCI outcomes in patients with severely calcified coronary artery disease. This study demonstrates potential benefits of IVL in reducing procedural failure and residual stenosis, possibly translating into lower rates of target vessel failure. However, slight increases in procedural complications and borderline statistical significance indicate that further evidence is needed. In clinical practice, IVL may be a technically advantageous and innovative tool for treating heavily calcified coronary lesions. Yet, its potential benefits and risks should be carefully weighed within the clinical context and lesion characteristics of each patient. In conclusion, IVL holds promise as a more effective and safer alternative to standard methods for treating calcified coronary lesions, but its role should be confirmed by larger randomized studies with extended follow-up periods.