Efficacy and Safety of an Upfront RotaTripsy Strategy in the Treatment of De Novo and In-Stent Restenosis Cases

Abstract

Background. Use of both rotational atherectomy (RA) and intravascular lithotripsy (IVL)—the “RotaTripsy” technique—offers a potentially synergistic calcium-modification strategy that can treat both luminal and abluminal calcification. An upfront RotaTripsy strategy using an undersized burr in large-caliber coronaries also offers the advantage of facilitating IVL catheter passage while being able to undertake the procedure with a 6-Fr system. Methods. Consecutive patients with heavily calcified lesions on angiographic or intravascular imaging and large target-vessel caliber (≥3 mm) who underwent an upfront RA followed by IVL between July 2021 and January 2022 were included in this study. Study aims were to evaluate periprocedural efficacy and safety. Results. Of the 21 patients included, RotaTripsy was used for treatment of de novo lesions in 12 patients (57%) and for in-stent-restenosis in 9 patients (43%). Seven cases of in-stent restenosis (ISR) involved 2 layers of stents. Mean reference vessel diameter was 3.67 ± 0.46 mm and baseline diameter stenosis was 77.4 ± 11.3%. Average RA burr-to-artery ratio was 0.43 ± 0.05 and IVL balloon-to-artery ratio was 0.93 ± 0.06, with IVL balloon crossing the lesion in all cases following RA. Procedural success was attained in 20 of 21 cases; 1 periprocedural complication (a death related to coronary perforation following stent postdilation) was recorded. Conclusions. An upfront RotaTripsy strategy is associated with a high degree of procedural success in de novo lesions and ISR cases by facilitating the use of a smaller burr-to-artery ratio and smaller-bore vascular access. Larger studies are required to further evaluate the potential benefits of an upfront RotaTripsy strategy from a safety and cost-benefit perspective.

Keywords: atherectomy, coronary calcification, intravascular lithotripsy, Rotablator

Listen to the accompanying podcast here.

Intracoronary calcification has been associated with an increased risk of stent underexpansion, malapposition, and disruption of drug polymer from stent surfaces hampering drug delivery and elution.^1,2 This leads to an increased risk of stent thrombosis and restenosis.³ To overcome these challenges, several techniques and equipment have been developed. High-pressure and ultra-high-pressure non-compliant balloons, cutting balloons, or scoring balloons are often used for mild to moderate calcification. For heavier burden of calcification, rotational atherectomy, orbital atherectomy, laser atherectomy, and more recently, intravascular lithotripsy (IVL), are tools with proven efficacy. IVL has afforded a novel method for overcoming deeply embedded calcium by inciting cracks from ultrasonic pressure waves, thereby facilitating stent expansion.⁴ However, a potential limitation of the IVL balloon catheter is the inability to cross significantly stenosed and heavily calcified lesions. While the DISRUPT-CAD III trial noted a very high success rate in their cohort of patients, the studied population vessel diameter stenosis may be significantly lower than seen in a real-world population. Current guidelines recommend rotational atherectomy in patients with fibrotic or heavily calcified lesions to improve procedural success and may be a useful initial step in the event an IVL balloon does not cross.⁵ The utilization of RA followed by IVL (the “RotaTripsy” technique) in large coronary arteries could potentially be synergistic, given the treatment of luminal and abluminal calcification. RA has been associated with a higher rate of complications, notably no flow, slow flow, perforations, and dissections, especially with the use of larger burrs.⁶ In addition, larger burr sizes necessitate the use of 7- and 8-Fr systems, which increase the risk of access-site complications.⁷ Whether these complications can be mitigated with the use of a smaller burr-to-artery ratio (≤1.75 burr) that can be utilized with a 6-Fr guide system followed by a 1:1 IVL balloon can be an effective, synergistic strategy for calcium modification in large coronary arteries remains unclear. We sought to investigate the safety and efficacy of an upfront strategy of RotaTripsy in order to overcome the limitations of these 2 calcium-modification therapies.

Methods

A single-center study assessing the feasibility, efficacy, and safety of RotaTripsy in heavily calcified coronary lesions was performed at a large, tertiary hospital (Mount Sinai Hospital, New York, New York) between July 2021 to January 2022. Inclusion criteria were patients with severe coronary calcification based on angiographic or intravascular imaging characteristics who underwent RA followed by IVL wtih a target-vessel diameter ≥3.0 mm. Both patients with de novo lesions and patients with in-stent restenosis (ISR) were included. Lesions were classified as severely calcified by angiography (tram track appearance) or by intravascular imaging (>270° arc of calcification). Patients underwent RA with RotaPro (Boston Scientific) followed by IVL with Shockwave C2 (Shockwave Medical).

Our standardized laboratory practice involving RA has been described in detail previously.⁸ Briefly, individual burring runs were kept at 15 to 20 seconds, with burr speeds of 140,000 to 150,000 rpm. An undersized burr caliber was used to facilitate IVL passage to conform to a 6-Fr sheath and guide catheter as opposed to the standardized 0.5-0.6 burr-to-artery sizing. Excessive burr decelerations of more than 5000 rpm from the platform speed were avoided by gentle, gradual burr advancement in a “pecking” fashion. Rotaflush with normal saline containing a cocktail of nitroglycerin (5 mg/L), verapamil (5 mg/L), and heparin (5000 U/L) was continuously infused through the Teflon Rotablator sheath throughout the procedure. The decision to dilate the lesion following Rotablator was at the operator’s discretion. The IVL catheter was then advanced over the operator’s choice of an 0.14-inch coronary guidewire sized 1:1 with the reference vessel diameter. The IVL balloon was first inflated to 4 atm at the target lesion with subsequent delivery of 10 IVL pulses followed by a short balloon inflation to 6 atm as per previously published protocol.⁹ IVL treatments were continued (up to 80 pulses) until full balloon expansion was achieved with interval deflations. Quantitative coronary angiography (QCA) was performed offline using a dedicated software QAngio XA, version 7.3 (Medis Medical Imaging System BV) to assess the preprocedure reference vessel diameter, percent diameter stenosis, and lesion length, as well as postprocedure residual diameter stenosis, by an experienced independent observer at the institutional core laboratory. The decision for the use of intravascular imaging and the type of imaging modality used (intravascular ultrasound [IVUS] or optical coherence tomography [OCT]) was largely based on operator preference. In cases of left main involvement, or when concerns of renal impairment were an issue, the institutional preference is to opt for IVUS over OCT.

All patients and procedure-related data were entered in the institutional registry within 24 hours of the index percutaneous coronary intervention (PCI). Patients enrolled in the registry provided consent for anonymized data collection and systematic follow-up and were prospectively followed by clinic visit or telephone call by dedicated research staff. The primary endpoints were angiographic success, procedural success, and successful delivery of IVL balloon. Procedural success was defined as angiographic success (final diameter stenosis of <30% with Thrombolysis in Myocardial Infarction [TIMI]-3 flow) in the absence of in-hospital major adverse cardiac event (MACE), defined as the composite of cardiac death, myocardial infarction, or target-vessel revascularization (TVR).

Results

During the study period, a total of 21 patients that met the inclusion criteria and underwent an upfront RotaTripsy strategy and were included in the analysis (mean age, 69.3 ± 8 years; 81% male). Baseline characteristics are reported in Table 1. Most patients (90.4%) underwent PCI for stable angina and 28.5% of patients had history of prior coronary artery bypass graft.

Procedural characteristics are summarized in Table 2. RotaTripsy was used for treatment of de novo lesions in 12 patients (57%) and for ISR in 9 patients (43%). Seven cases of ISR involved 2 layers of stents. The target coronary segment was proximal in 71.4% of cases. The procedure was performed via femoral access in 71.5% of patients. An upgrade to a 7-Fr system was required in 1 patient who underwent mini-crush bifurcation stenting. Intracoronary imaging (IVUS or OCT) was utilized in 47.6% of patients.

Mean reference vessel diameter was 3.67 ± 0.46 mm, with a mean lesion length of 28.9 ± 12.7 mm. Baseline diameter stenosis was 77.4 ± 11.3%. Burr sizes of 1.75 mm, 1.5 mm, and 1.25 mm were used in 52.5%, 38%, and 9.5% of patients, respectively. Average RA burr-to-artery ratio was 0.43 ± 0.05 and the IVL balloon-to-artery ratio was 0.93 ± 0.06. During the procedure, the mean number of IVL pulses delivered was 53.8 ± 20.11. A drug-eluting stent was deployed in all patients with de novo lesions and in 2 of the cases of single-stent ISR. Representative cases with angiography and intracoronary imaging are shown in Figure 1 and Figure 2.

Angiographic success and IVL balloon crossing following RA was achieved in 21 cases (100%). Procedural success was attained in 20 of 21 cases (95.2%). One death related to frank coronary perforation occurred following stent postdilation with a non-compliant balloon in a heavily calcified, severely stenosed, and tortuous right coronary artery.  Intravascular imaging was not performed upfront due to severity of calcification and stenosis. Following stent deployment, postdilation was performed due to mild underexpansion in the proximal segment of the vessel that corresponded to the segment of adventitial calcium. This resulted in an Ellis 3 perforation, which required covered stent implantation and was further complicated by persistent no reflow and cardiogenic shock.

No postprocedure vascular complications or strokes were recorded in the immediate postprocedure period or at 1 month.

Discussion

Combining RA and IVL was first published by Jurado-Roman et al, and case series of the combination have been recently published.^10,11 However, these case series used IVL as a bail-out technique rather than as an upfront strategy. Despite advances in PCI techniques, stent technology, and pharmacotherapy, patients undergoing PCI for calcified lesions experience a higher MACE rate.¹² IVL is fast becoming an established therapy for the management of severely calcified coronary lesions due to its ease of use and favorable safety profile. However, as noted by the authors of the DISRUPT CAD-II study, atherectomy remains a front-line therapy, particularly in the event where even low-profile balloons do not cross.¹³ In addition, in DISRUPT CAD III, the use of atherectomy devices to facilitate crossing of the IVL balloon catheter was prohibited. Although an inability to pass the IVL balloon across the target lesions was only observed in 1.8% of patients in the DISRUPT III trial, this likely represents selection bias. For instance, the percent diameter stenosis in the DISRUPT-CAD III study was 65.1 ± 10.8% compared with 77.37 ± 11.27% observed in the present study. As such, it is likely that real-world utilization necessitating the synergistic use of RA and IVL will likely be much greater in an unselected patient cohort.⁹

Additionally, the present study presents the feasibility and success in patients undergoing IVL in cases with ISR, which has not been specifically evaluated in either landmark RA trials or the IVL trials. Future studies are needed to confirm the feasibility of this technology in this patient population.

Complications related to a larger burr-to-artery ratio are well known and aggressive strategies utilizing larger RA burr sizes (>0.70 burr-to-artery ratio) have historically held no advantages over less aggressive burr sizes (≤0.70 burr-to-artery ratio) with a higher risk of complications including periprocedural myocardial infarction and target-lesion revascularization.^6,14 In addition, utilization of 2.0-mm and 2.15-mm burrs requires 7-Fr and 8-Fr systems, which have been independently associated with higher complications.⁷ Our study utilized a significantly smaller burr-to-artery ratio of 0.43 ± 0.05 in a relatively larger reference vessel size with a high degree of stenosis with the procedure successfully completed with a 6-Fr guide system in most cases. The observed death in this study also highlights the recognized challenges of PCI in patients with severe coronary artery calcification.¹⁵

Study limitations. Potential limitations to our study include the relative underutilization of intravascular imaging, which could further aid in a tailored approach to managing patients with heavy calcification. Despite a high efficacy rate and favorable safety profile, the limited number of patients precludes the broad generalization of our results. The authors concede that there is a significant increase in the cost of utilizing both RA and IVL. However, whether this can be balanced by the favorable safety profile will need to be evaluated in larger clinical trials.

Conclusion

Our study demonstrates that an upfront RotaTripsy strategy is associated with a high degree of procedural success in both de novo lesions and in patients with ISR by facilitating the use of a smaller burr-to-artery ratio and smaller-bore vascular access. Larger studies are required to further evaluate the potential benefits of an upfront RotaTripsy strategy from a safety perspective and cost-benefit analysis.

Affiliations and Disclosures

From ¹the Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York; and ²Department of Cardiology and the University of Melbourne, Austin Health, Melbourne, Australia.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Sharma reports speaker’s honoraria from Boston Scientific. The remaining authors report no conflicts of interest regarding the content herein.

The authors report that patient consent was provided for publication of the images used herein.

Manuscript accepted November 29, 2022.

Address for correspondence: Samin K. Sharma, MD, The Zena and Michael A. Weiner Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1030, New York, NY 10029-6574. Email: samin.sharma@mountsinai.org

References

1. Kini AS, Vengrenyuk Y, Pena J, et al. Optical coherence tomography assessment of the mechanistic effects of rotational and orbital atherectomy in severely calcified coronary lesions. Catheter Cardiovasc Interv. 2015;86(6):1024-1032. Epub 2015 May 11. doi:10.1002/ccd.26000

2. Wiemer M, Butz T, Schmidt W, Schmitz K-P, Horstkotte D, Langer C. Scanning electron microscopic analysis of different drug eluting stents after failed implantation: from nearly undamaged to major damaged polymers. Catheter Cardiovasc Interv. 2010; 75(6):905-911. doi:10.1002/ccd.22347

3. Madhavan MV, Tarigopula M, Mintz GS, Maehara A, Stone GW, Généreux P. Coronary artery calcification: pathogenesis and prognostic implications. J Am Coll Cardiol. 2014;63(17):1703-1714. Epub 2014 Feb 12. doi:10.1016/j.jacc.2014.01.017

4. Brinton TJ. Ali ZA, Hill JM, et al. Feasibility of Shockwave coronary intravascular lithotripsy for the treatment of calcified coronary stenoses. Circulation. 2019;139(6):834-836. doi:10.1161/CIRCULATIONAHA.118.036531

5. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI Guideline for coronary artery revascularization: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145(3):e4-e17. Epub 2021 Dec 9. doi:10.1161/CIR.0000000000001039

6. Whitlow PL, Bass TA, Kipperman RM, et al. Results of the study to determine Rotablator and transluminal angioplasty strategy (STRATAS). Am J Cardiol. 2001;87(6):699-705. doi:10.1016/s0002-9149(00)01486-7

7. Grossman PM, HS Gurm, McNamara R, et al. Percutaneous coronary intervention complications and guide catheter size: bigger is not better. JACC Cardiovasc Interv. 2009;2(7):636-644. doi:10.1016/j.jcin.2009.05.012

8. Doshi SN, Kini A, Kim MC, et al. A comparative study of rotational atherectomy in acute and stable coronary syndromes in the modern era. Am J Cardiol. 2003;92(12):1404-1408. doi:10.1016/j.amjcard.2003.08.045

9. Hill JM, Kereiakes DJ, Shlofmitz RA, et al; for the Disrupt CAD III Investigators. Intravascular lithotripsy for treatment of severely calcified coronary artery disease. J Am Coll Cardiol. 2020;76(22):2635-2646. Epub 2020 Oct 15. doi:10.1016/j.jacc.2020.09.603

10. Jurado-Román A, Gonzálvez A, Galeote G, Jiménez-Valero S, Moreno R. RotaTripsy: combination of rotational atherectomy and intravascular lithotripsy for the treatment of severely calcified lesions. JACC Cardiovasc Interv. 2019;12(15):e127-e129. Epub 2019 Jul 17. doi:10.1016/j.jcin.2019.03.036

11. Buono A, Basavarajaiah S, Choudhury A, et al, et al. “RotaTripsy” for severe calcified coronary artery lesions: insights from a real-world multicenter cohort. Cardiovasc Revasc Med. 2021;37:78-81. Epub 2021 Jul 2. doi:10.1016/j.carrev.2021.06.132

12. Copeland-Halperin RS, Baber U, Aquino M, et al. Prevalence, correlates, and impact of coronary calcification on adverse events following PCI with newer-generation DES: findings from a large multiethnic registry. Catheter Cardiovasc Interv. 2018;91(5):859-866. Epub 2017 Jul 19. doi:10.1002/ccd.27204

13. Ali ZA, Nef H, Escaned J, et al. Safety and effectiveness of coronary intravascular lithotripsy for treatment of severely calcified coronary stenoses: the Disrupt CAD II study. Circ Cardiovasc Interv. 2019;12(10):e008434. Epub 2019 Sep 25. doi:10.1161/CIRCINTERVENTIONS.119.008434

14. Safian RD, Feldman T, Muller DW, et al. Coronary angioplasty and Rotablator atherectomy trial (CARAT): immediate and late results of a prospective multicenter randomized trial. Catheter Cardiovasc Interv. 2001;53(2):213-220. doi:10.1002/ccd.1151

15. Guedeney P, Claessen BE, Mehran R, et al. Coronary calcification and long-term outcomes according to drug-eluting stent generation. JACC Cardiovasc Interv. 2020;13(12):1417-1428. doi:10.1016/j.jcin.2020.03.053