Complementary Utility of Intravascular Lithotripsy With Atherectomy for Severely Calcified Coronary Stenoses in Contemporary Practice

Abstract

Background. The effectiveness and safety of a contemporary combined approach that incorporates the novel intravascular lithotripsy (IVL) technology into conventional tools including atherectomy have yet to be studied. Methods. We retrospectively included consecutive patients who underwent percutaneous coronary intervention (PCI) with IVL from March 2021 to February 2022. Effectiveness (residual stenosis of <30%) and safety outcomes (procedural complications and major adverse cardiovascular event [MACE] defined as a composite of all-cause death, myocardial infarction, or target vessel revascularization) were compared between patients undergoing IVL with and without atherectomy. Results. A total of 109 patients underwent IVL, of whom 33 patients (30.3%) were treated with both IVL and atherectomy and had higher risk features including reduced cardiac function and more frequent use of mechanical circulatory support. Angiographic success for calcified de novo lesions was achieved in 85.7% and 90.6% of the combined and non-atherectomy groups, respectively (P=.49). Each group had one case of coronary perforation (P=.52) while major dissection occurred in 2 cases of calcific stent underexpansion in the combined group (6.1% vs 0%; P=.09). Thirty-day MACE occurred in 4.8% of patients including 3 deaths in the atherectomy group and 1 cardiac death and 1 myocardial infarction in the non-atherectomy group (P=.16). Conclusion. Procedural success and complications were similar in patients undergoing IVL with and without atherectomy when treating calcified de novo lesions. Those who required a combined approach represented a high-risk population with high mortality, suggesting that a multidisciplinary approach is needed to optimize case selection and care beyond PCI.

Keywords: percutaneous coronary intervention, coronary calcification, intravascular lithotripsy, rotational atherectomy, orbital atherectomy, excimer laser coronary atherectomy

Calcified coronary lesions have traditionally been treated with balloon angioplasty with normal or specialty balloons, atherectomy devices including rotational atherectomy (RA), orbital atherectomy (OA), and excimer laser coronary atherectomy (ELCA), or a combination of these techniques.¹ Intravascular imaging allows us to select an appropriate tool based on the extent of calcification and facilitates adequate lesion preparation prior to stenting.² It is, however, not uncommon to encounter complex calcified lesions that prevent full stent expansion despite multiple attempts of calcium modification using different tools. Resultant stent underexpansion is associated with stent failure and poses technical challenges to repeat revascularization because there are no established, effective strategies for calcium modification behind the underexpanded stent.³

Recently, the United States Food and Drug Administration (FDA) approved a novel non-atherectomy device (Shockwave Intravascular Lithotripsy [IVL] System; Shockwave Medical, Inc) that leverages an established technique for the treatment of kidney stones. The IVL catheter generates pulsatile sonic pressure waves that can induce microfracture both in deep and superficial calcium, thereby facilitating lesion expansion. Recent prospective studies validated its effectiveness for calcified de novo lesions with a low rate of procedural complications and satisfactory 1-year clinical outcomes.^4-8 Therefore, with its innovative, unique mechanism of action, IVL may help decrease the overall incidence of suboptimal stent expansion and improve outcomes in this complex lesion subset. However, the strict inclusion and exclusion criteria used in these studies limit generalizability to real-world clinical scenarios. For example, the use of scoring/cutting balloons (SB/CB) or atherectomy devices was not permitted as adjuvant therapy to purely assess the efficacy of IVL. In daily clinical practice, the combined use of available tools under the guidance of intravascular imaging is considered the most effective approach when treating complex calcified stenoses.^1,2 Nevertheless, the effectiveness and procedural risks of such a combined approach that incorporates the novel IVL technology into our conventional strategy has yet to be studied. Accordingly, we evaluated the complementary utility and safety of IVL with atheroablative devices for the treatment of severely calcified lesions in contemporary, real-world practice.

Methods

Study population. This observational study included consecutive patients who underwent percutaneous coronary intervention (PCI) with Shockwave IVL for severely calcified de novo lesions as well as calcific underexpanded stents from March 2021 to February 2022 at 2 tertiary care hospitals (Montefiore Medical Centers Moses and Weiler Hospitals, Bronx, New York). The included patients were divided into 2 groups based on the combination of different tools: (1) patients treated with the combined use of IVL and atherectomy; and (2) those treated with non-atherectomy approaches (ie, IVL and balloon angioplasty). This study complied with the Declaration of Helsinki and was approved by the Montefiore-Einstein institutional review board.

Procedures. Details on the Shockwave system and catheter are described elsewhere.⁶ Briefly, the IVL catheter is a 6-Fr compatible, semi-compliant balloon used over a 0.014-inch guidewire. The balloon was positioned across the lesion and inflated to 4 atm to ensure apposition to the vessel wall. Then, the IVL catheter was connected to the IVL generator to deliver a cycle of 10 pulses at a frequency of 1 pulse/second. The balloon was then inflated to 6 atm depending on operator preference, and the therapy could be repeated up to 8 cycles depending on the lesion characteristics and response to IVL.

PCI was performed with standard interventional techniques and with drug-eluting stent (DES) implantation. Pre- and post-IVL calcium modification with non-compliant balloon (NCB), SB, CB, or atherectomy devices was performed at the discretion of operators, followed by DES implantation and postdilation with NCB. All patients received optimal antiplatelet therapy in accordance with contemporary guidelines.

Angiographic and clinical outcomes. Device success was defined as successful completion of IVL crossing and therapy delivery without immediate serious complications such as severe dissection, perforation, or slow flow/no reflow. Angiographic success was defined as residual stenosis of <30% with Thrombolysis in Myocardial Infarction (TIMI) 3 flow, which is the same angiographic endpoint used in the previous validation studies.^4-6Major adverse cardiac event (MACE) was defined as a composite of all-cause death, myocardial infarction (MI), or target-vessel revascularization (TVR). All clinical data including clinical follow-up were retrospectively collected by medical chart review. Coronary angiography was analyzed by an experienced interventional cardiologist not involved in any of the procedures.

Statistical analysis. Continuous variables are expressed as mean ± standard deviation. Normality of continuous variables was confirmed with the Shapiro-Wilk test. Continuous variables with normal distribution were compared with the Student’s t test or Welch’s t test depending on the result of the Levene’s test for equality of variances. If the normality test failed, the Mann-Whitney test was used. Categorical variables are presented with frequency and percentage and were compared with the Chi-squared test or Fisher’s exact test as appropriate. A 2-sided P-value <.05 was considered statistically significant. All statistical analyses were conducted using IBM SPSS Statistics, version 28 (IBM Corp). Sankey diagrams were created based on the d3-sankey plugin.⁹

Results

Baseline characteristics. From March 2021 to February 2022, a total of 109 patients underwent PCI with IVL (Table 1). Among those, 33 patients (30.3%) were treated with both IVL and atherectomy. The overall cohort had a mean age of 71.2 ± 10.9 years with 41% women and multiple comorbidities including chronic kidney disease (46.8%) or end-stage renal disease on hemodialysis (15.6%). Furthermore, a high prevalence of previous revascularization (58.7%) and LVEF ≤50% (41.3%) was observed, with two-thirds of the included patients presenting with acute coronary syndrome.

When comparing baseline characteristics between the 2 groups, patients who were treated with the combined strategy had a trend toward a higher prevalence of prior MI (36.4% vs 25.0%) and LVEF ≤50% (54.5% vs 38.6%), while chronic kidney disease (51.3% vs 36.4%) and peripheral artery disease (18.4% vs 9.1%) were numerically more prevalent in the non-atherectomy group .

Angiographic and procedural characteristics. A calcified de novo lesion in the left anterior descending coronary artery was the most common lesion type and location in both groups (Table 2). Approximately 15% of cases were treated for stent underexpansion due to underlying severe calcification. PCI for unprotected left main coronary artery stenosis was performed in 7.3% of patients.In patients who underwent IVL with atherectomy, mechanical circulatory support was more frequently used during the procedure (24.2% vs 10.5%) as PCI was considered high risk (Table 2). In addition, a 7-Fr guiding catheter via the femoral artery was the most common approach in those patients, whereas a 6-Fr guiding catheter via the radial artery was most used in the non-atherectomy group. It is notable that PCI was performed with the guidance of intravascular imaging in all patients, except 1 case where the IVUS catheter could not cross the lesion despite predilation with NCB and the use of a guide extension catheter. All patients underwent post-stent dilation with NCB.

Revascularization approach. Figure 1A summarizes the treatment approaches that led to device success for calcified de novo lesions. IVL was selected as the initial therapy in 22% of patients while pre-IVL intervention was performed in the rest of the patients. The reason for IVL following other techniques was to facilitate IVL catheter delivery or due to incomplete lesion preparation with the initial strategy. Most patients (69%) underwent further lesion preparation primarily with NCB or specialty balloons to ensure sufficient balloon expansion before DES implantation. Figure 1B shows the treatment approaches used for stent underexpansion due to underlying calcification, with 2 out of 17 cases treated with bail-out IVL for acutely underexpanded stents. Similar to those for de novo lesions, other tools were initially used for IVL catheter delivery, or subsequent use of IVL was needed due to insufficient preparation with NCB or ELCA (Figure 2).

Angiographic outcomes. Device success was achieved in nearly all patients (97.0% in the combined group and 96.1% in the non-atherectomy group; P>.99) (Table 3). Overall angiographic success of the combined and non-atherectomy groups was 78.8% and 89.5%, respectively (P=.14). When IVL was used for calcified de novo lesions, angiographic success was comparable in both groups (85.7% in the combined group and 90.6% in the non-atherectomy group; P=.49). When using an effective endpoint defined in the Disrupt CAD III study (ie, <50% residual stenosis), overall angiographic success was higher (90.9% and 90.8% in the combined and non-atherectomy groups, respectively; P>.99). Major dissection was observed in 2 patients in the combined group after IVL or ELCA, both of which were used for calcific underexpanded stents. Coronary perforation occurred in 2 cases due to IVL balloon rupture and high-pressure dilation of NCB after IVL in the non-atherectomy and combined groups, respectively. Both cases were treated with a covered stent.

Clinical outcomes. In-hospital MACE occurred in 3.7% of all patients, consisting of 4 cardiac deaths with no MI or TVR (Figure 3). The incidence of death was numerically higher in the combined group compared with the non-atherectomy group (9.1% vs 1.3%; P=.08). One death in each group was due to cardiogenic shock despite successful revascularization. The second death in the combined group was related to coronary perforation occurring during high-pressure dilation with NCB, which led to right ventricular dysfunction and cardiogenic shock. The third death in the combined group occurred 1 month after coronary artery bypass grafting for significant stenosis in the proximal left anterior descending coronary artery following successful PCI in the right coronary artery.

Clinical outcomes through 30 days were available in 104 patients (95.4%) (Figure 3). The cumulative incidence of MACE at 30 days was 4.8% (5 patients) including 3 deaths in the combined group (2 cardiac and 1 non-cardiac deaths) and 1 cardiac death and 1 MI in the non-atherectomy group. There was no TVR within 30 days after the index procedure.

Discussion

The present study evaluated the effectiveness and safety of the combined use of IVL with atherectomy devices in a real-world population with severely calcified coronary stenoses and those with stent underexpansion due to underlying calcification. The principal findings of this investigation are as follows: (1) the combined use of IVL with atherectomy allowed effective calcium modification under the guidance of intravascular imaging with similar device and angiographic success between patients who underwent IVL with and without atherectomy; (2) procedural complications in the combined group were comparable to those in the non-atherectomy group when treating calcified de novo lesions; and (3) in-hospital mortality was higher in patients treated with both IVL and atherectomy, who represented a subset of patients with higher-risk features, such as impaired cardiac function and use of mechanical circulatory support devices during PCI.

The Disrupt CAD III study is currently the largest prospective, single-arm study supporting the usefulness of IVL for calcified de novo coronary lesions.⁶ A total of 431 patients were treated with IVL but without the adjuvant use of SB/CB or atherectomy. Angiographic success was 96.4%, with in-hospital, 30-day, and 1-year MACE rates of 7.0%, 7.8%, and 13.8%, respectively, which met the primary effectiveness and safety endpoints of the study.⁷ Of note, MACE was largely driven by periprocedural MI or non-Q-wave MI, and cardiac death was observed in 4 out of 373 patients (1.1%) at 1 year. These satisfactory clinical outcomes are comparable to the results of the ORBIT II (Evaluate the Safety and Efficacy of Orbital Atherectomy System in Treating Severely Calcified Coronary Lesions) trial that has a similar study design,¹⁰ supporting the clinical utility of IVL as a non-atherectomy tool. It is, however, notable to mention that a single technique is not always sufficient to achieve optimal lesion preparation in daily clinical practice. Rather, a combination of different tools under the guidance of intravascular imaging is often required and commonly advocated to ensure effective calcium modification and presumably to avoid complications as a result of the aggressive use of a single technique.^1,2 Nevertheless, such a combined approach is currently supported by several case reports only,^11,12 and the complementary utility of IVL with atherectomy has never been fully studied in contemporary practice. In the light of this background, we evaluated the effectiveness and safety of the combined use of IVL with atherectomy in a high-risk cohort that had more comorbidities and more angiographically complex lesions, such as those with a bifurcation lesion involving unprotected left main coronary artery or requiring mechanical circulatory support during PCI as compared with patients enrolled in the Disrupt CAD III study. These characteristics can adversely affect procedural success and clinical outcomes.^13,14 Moreover, approximately 75% of patients included in the present study would have been excluded in the Disrupt CAD III study not simply because of the adjuvant use of atherectomy devices, but also because of baseline characteristics, such as lesion severity, end-stage renal disease, and acute coronary syndrome. Nevertheless, a combination of available techniques including IVL allowed us to achieve a success rate as high as those seen in previous feasibility studies.^4-6 Moreover, serious procedural complications seen in the combined group included 1 coronary perforation during NCB dilation in a de novo lesion and 2 major dissections in cases with calcific stent underexpansion, indicating that incorporating the novel IVL technology into our conventional strategy appears to be safe and feasible, especially in treating calcified de novo lesions.

To the best of our knowledge, the present study is the largest report of real-world data supporting the clinical utility of IVL in contemporary practice. It is noteworthy that our revascularization strategy was guided by intravascular imaging in all patients with an intravascular imaging-crossable lesion, whereas the use of IVUS/optical coherence tomography (OCT) was limited to 30%-50% in prior observational studies.^15-20 The use of intravascular imaging is recommended in the current guidelines and is particularly important in the context of calcified lesions.^2,21-24 Thus, we believe that intravascular imaging helped us optimize PCI and achieve satisfactory angiographic outcomes comparable to other real-world data despite the fact that the present study included a medically and anatomically complex group of patients. However, we must emphasize that mortality in a high-risk population—such as those with cardiogenic shock—remains high despite successful PCI, as shown in large-scale registries.^13,14 Our results suggest that those who require both IVL and atherectomy are more likely to have clinical and angiographic factors that impact mortality, such as reduced left ventricular function and poor hemodynamic status.²⁵ When treating these high-risk cases, a multidisciplinary heart team approach is essential to optimize both case selection and care beyond PCI to improve patient outcomes, as endorsed by the current guideline.²¹ Furthermore, additional research is needed to identify a specific subset of high-risk patients in whom PCI with the combined approach leads to a clinically relevant improvement in outcomes.

Study limitations. Our results should be interpreted with some important limitations. First, due to the observational nature of the present study, there are potential biases that may have impacted the selected strategy. Second, the present study lacks quantitative assessment using intravascular imaging, which would have allowed more comprehensive evaluation and comparisons between the 2 groups. Future research is required to clarify the IVUS or OCT findings that would indicate IVL after atherectomy. Third, the type(s) of lesion that require post-IVL lesion preparation have not yet been ascertained. Interestingly, although one would expect that OCT should visualize therapeutic effects of IVL, the absence of calcium fracture did not affect subsequent stent expansion in the Disrupt CAD III study.⁶ This result indicates that microfracture induced by IVL is likely beyond the resolution of OCT and intravascular imaging may not help determine the indication of post-IVL lesion preparation. Based on our experience, balloon angioplasty with NCB or SB/CB is recommended after IVL if full expansion of the IVL balloon cannot clearly be observed during IVL treatment. If IVL is used after observed underexpansion of the NCB or SB/CB, reusing these balloons after IVL may allow us to see the impact of IVL on the calcified lesion. Fourth, although IVL could theoretically be a safer alternative to other options, such as ELCA with contrast injection, RA, or OA for calcific stent underexpansion,^26-29 the use of IVL for such lesions is still off-label and appears to be less effective than when used for calcified de novo lesions.^15,18,30 Additionally, there are possible concerns such as drug-polymer damage and the resultant risk of delayed endothelial coverage, stent thrombosis, and in-stent restenosis, especially if IVL is used for acutely underexpanded stents.³⁰ A recent report by Mastrangelo et al highlighted a high rate of TVR (34.8%) during a median follow-up of 12 months after successful IVL for calcific stent underexpansion.¹⁸ Although overall procedural success was satisfactory in the present and prior observational studies, particularly if the complexity of the lesions is considered, future research is needed to assess mid- to long-term outcomes after IVL treatment for undilatable underexpanded stents with peristent calcium. Lastly, OA was less frequently used in the present study compared with other atherectomy devices, indicating that our result may not be generalizable to calcified lesions initially treated with OA.

Conclusion

Procedural success and complications were similar in patients who underwent IVL with and without atherectomy under the guidance of intravascular imaging, supporting the feasibility of its complementary use with conventional technologies. Those who require both IVL and atherectomy may represent a high-risk population with high mortality and should be managed with a multidisciplinary approach to optimize case selection and care beyond PCI.

Affiliations and Disclosures

From the ¹Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York; ²Division of Cardiology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York; ³Division of Cardiology, White Plains Hospital, White Plains, New York; and the ⁴Cardiovascular Research Foundation, New York, New York.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Latib has served on advisory boards or as a consultant for Medtronic, Boston Scientific, Philips, Canon, CorFlow, NuevoSono, Bolt Medical, and Abbott. The remaining authors report no conflicts of interest regarding the content herein.

Manuscript accepted October 28, 2022.

Address for correspondence: Azeem Latib, MD, Section Head, Interventional Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 1825 Eastchester Road, Bronx, NY 10461. Email: alatib@gmail.com

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