Background/Purpose: Calcified coronary lesions restrict stent delivery and expansion during percutaneous coronary intervention (PCI). Intravascular Lithotripsy (IVL /Shockwave Medical) is a novel tool that treats coronary calcification. However, standalone IVL may be inadequate and combination with rotablation (rotashock) may be required.We performed detailed analysis of “rotashock” patients.

Materials/Methods: We conducted retrospective analysis of the PCI database from 2 United Kingdom (UK) centres (2018–2020). Patients who underwent rotashock therapy were analysed for patient and procedural characteristics and compared to those who underwent IVL. All patients had intracoronary imaging.

Results: Eighty eight patients were included in the analysis. One third of the patients (29.5%, n=26) underwent rotashock therapy. Patients who underwent rotashock more likely had hypercholesterolemia (65.4% versus 35.5%, p=0.01) and significantly more angiographic calcification assessed by the Birmingham Calcium Score (BCS: 0: wall calcification; 1: luminal spiculated calcium, 2: focal intraluminal calcium <1/2 vessel diameter and 3: focal intraluminal calcium ≥1/2 vessel diameter) (rotashock: BCS 2/3 96.2% versus IVL alone: BCS 2/3 61.3%, p=0.001). BCS correlated with Intra Coronary imaging (Kendall’s tau 0.34, p=0.02). Procedural complication rates (burst IVL balloon, Ellis 3 perforation, side branch occlusion, stent fracture, retained microcatheter tip) were no different between the groups (rotashock 11.5% versus IVL alone 14.5%, p= ns). No major complications such as death, myocardial infarction, stroke or referral for emergency bypass graft surgery occurred.

Conclusions: Rotashock can be safely performed with a low rate of in-hospital complications. BCS may help guide choice of tool for calcium modification in addition to intracoronary imaging.

Sharma V, Rahman M, Elangovan SK, Yuan M, ’Kane PO, et al. Rotashock Therapy: An Observational Study. J Cardiol Clin Res. 2021; 9(2): 1169

Calcium modification; IVL@; Rotashock; Rotablation

Coronary artery calcification is a marker of cardiovascular risk [1,2], and is influenced by Diabetes Mellitus (DM), age, gender, hypertension (HTN), and chronic kidney disease (CKD) [3].

The presence of a calcified coronary lesion restricts balloon and/or stent delivery and expansion during percutaneous coronary intervention (PCI). This increases the subsequent risk of in-stent restenosis, stent thrombosis and total occlusion of the vessel [4]. Assessment of the degree of calcification of the coronary lesion is influences the choice of tool for calcium modification.

Conventional tools to modify calcified coronary plaque include rotablation, cutting and scoring balloons. This may be inadequate for extensive and deep coronary calcification. Intravascular Lithotripsy (IVL) (Shockwave Medical Inc., Santa Clara, CA) is a novel tool that aids in tackling deep coronary calcification with the help of sonic pressure waves. It is a single use, monorail balloon which delivers local shockwave energy at low pressure inflations (4-6 atmospheres) of the balloon [5-8].

The use of IVL alone for the treatment of calcified coronary lesions has been studied in both research trials and observational analysis [9-12]. However, this single calcium-modification modality may be insufficient to treat heavily calcified coronary lesions and a combination of two different modalities may be required such as rotablation plus IVL (rotashock or rotatripsy), to tackle the coronary calcification, especially in vessels with deep calcification.

Data on the use of more than one calcium modification tool is limited [13]. We present a detailed observational analysis of patients who underwent rotashock therapy or IVL alone from two UK centres. All patients underwent intracoronary (I/C) imaging.

We conducted retrospective analysis of the PCI database and clinical records from two high volume UK PCI centres between 2018 and 2020. Operators at the two centres are well versed with rotablation and use of the novel IVL therapy. All patients included underwent I/C imaging with either Optical Coherence Tomography (OCT, Abbott Dragonfly OPTIS@) or Intravascular Ultrasound (IVUS, iLAB, Boston Scientific Corporation@ or Volcano Corporation@).

Local governance standards were adhered to and study was conducted according to the principles of the Declaration of Helsinki [14], and adhered to “Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting observational studies” [15].

Standard PCI techniques were utilised and the need for IVL or rotablation upfront was decided by the operator based on coronary angiographic calcification, and/or extent of calcification on intracoronary (I/C) imaging and/or failure of the pre-dilatation balloon to expand. The additional use of IVL post rotablation was decided by the operator based on inadequate balloon expansion post rotablation and/or inadequate calcium modification on intra-coronary imaging (lack of fracture of calcium arc or increased depth of calcium).

All patients were pre-treated with aspirin plus one other antiplatelet agent (clopidogrel, ticagrelor or prasugrel). The newer antiplatelet agents were utilised in patients who presented with acute coronary syndrome (ACS). Unfractionated Heparin (UFH) was utilised during the procedure and operators maintained activated clotting time (ACT) ~300 seconds during PCI. Patients who did not have intra-coronary imaging, those in whom the OCT/IVUS images were not available for off-line analysis and those in whom imaging was performed only after stent implantation were excluded.

Angiographic assessment of coronary calcification

Angiographic coronary calcium was graded independently by three experienced Interventional Cardiologists (VS, VK and CV) during the retrospectively analysis as per the Birmingham Calcium Score (BCS-developed “in-house”): score 0, 1, 2 or 3 (Figure 1). BCS: 0= coronary wall calcification with no visualised calcification within the lumen during cine acquisition with contrast, 1= spiculated calcium within the lumen during cine acquisition with contrast, 2= calcium protruding into the lumen <1/2 vessel diameter during cine acquisition with contrast, 3= calcium protruding in the lumen ≥1/2 the lumen diameter during cine acquisition with contrast. The PCI artery was viewed in all available cine views and the highest calcium score (Figure 1) was applied.

Intracoronary imaging assessment of coronary calcification

Calcification on OCT or IVUS was graded according to the arc (0-90, >90-180, >180-270 and >270- 360), depth (in mm, leading edge to leading edge) and length (in mm) of calcium.

Statistical analysis

Continuous variables are presented as mean (±SD), or median (range), and compared with student’s t test or Mann-Whitney test. Categorical variables are presented as percentage and compared with chi square test. Univariate analysis was performed between those who underwent rotashock and those who underwent IVL therapy alone for patient characteristics, angiographic and procedural characteristics and complications. The following patient characteristics were compared: age, gender, hypertension (HTN), diabetes mellitus (DM), hypercholesterolemia, previous MI or previous Ischemic Heart Disease (IHD), previous PCI, previous CABG, history of cerebrovascular disease, chronic kidney disease (CKD: eGFR<60ml/min/1.72m2 ). Variables with missing data were not included in the analysis.

In addition the BCS score was assessed for correlation with the I/C calcification score [16], in the subset of patients without previous stent and ISR.

Eighty eight patients were included in the analysis. The flow diagram (Figure 2), demonstrates patients who were included.

Median age was 75 years (range 67.5-79.5), 25% were female (n=22) and 35.2% had a diagnosis of DM (n=31). One third of the patients (29.5%, n=26) underwent rotashock treatment and twothirds underwent IVL therapy alone (70.5%, n=62).

Patients who underwent rotashock treatment, more frequently had a history of hypercholesterolemia compared to those who underwent IVL alone (65.4 % versus 35.5%, p=0.01, Table 1). Other demographics and cardiovascular risk factors were similar in the two groups (Table 1).

Angiographic calcification as assessed by BCS was significantly more severe in the rotashock group compared to the IVL alone group (rotashock BCS 2/3: 96.2% versus IVL alone BCS 2/3: 61.3%, p=0.001, Table 2). Mean arc, depth and length of calcium on combined IVUS and OCT I/C imaging was not significantly different between the groups (Table 3). However, depth of calcium was significantly more on OCT than IVUS (Supplementary table).

Moderate positive correlation was noted between BCS calcium score and I/C calcium score in patients who underwent OCT (Table 4).

The commonest PCI artery was the Left Anterior Descending (LAD) (Table 2). A third of the patients who underwent IVL required it for under-expanded previous stent or ISR (rotashock: 0% vs IVL 33.9%, p=0.001).

Procedural success rate (residual stenosis <30%) was no different in both groups despite the IVL balloon bursting (rotashock 7.7% versus IVL alone 8.1 %, p=0.77, Table 2). Procedural complication rates were low and no different between the groups (Table 2). Complications observed included burst IVL balloon, burst non-compliant balloon, retained corsair micro catheter tip, stent fracture, Ellis 3 perforation and side branch occlusion (table 2 for details).

No major in-hospital complications such as in-hospital death, MI, stroke or referral for emergency CABG were observed in either group.

Contrast use and fluoroscopy dose (Table 2), were similar in the two groups. Procedure time was significantly prolonged in the rotashock group compared to the IVL alone group (rotashock: 139.7 (±43.1) minutes versus IVL: 115.8 (±38.3) minutes, p=0.01, Table 2). Patients who underwent rotashock did not did not receive >80 pulses (use > 1 IVL balloon) compared to those who had IVL therapy alone (Table 2). Other procedural characteristics were no different between the two groups (Table 2).

Table 1: Baseline and angiographic characteristics

Table 2: Angiographic and Procedural Characteristics.

Table 3: Intracoronary Calcification on Intra Coronary imaging for the two groups.

Table 4: Correlation between BCS and I/C imaging score on OCT.

This retrospective study demonstrates that rotashock therapy is safe and effective. Rotashock patients had higher angiographic BCS severity of calcification had a low incidence of in- hospital complication rates.

Angiographic coronary calcification has been utilised to quantify the severity of calcification [5,6], and published data supports moderate correlation between angiographic calcification and arc/ length of calcium on intra-coronary imaging [6]. Assessment of the coronary angiogram to visually classify the severity of calcification may have a role in the choice of calcium modification tools.

Indeed, angiographic coronary calcification severity (assessed subjectively) was the main inclusion criteria in the major trials of IVL (DISRUPT CAD II [10], and DISRUPT CAD III study [18]). In an attempt to objectively assess angiographic calcification, we developed the “Birmingham Calcium Score” (BCS, Figure 1), and have utilised this in the assessment of angiographic calcification [7]. We demonstrated correlation of BCS with OCT I/C calcification score in our study patients.

In our patient cohort, the criteria that resulted in use of IVL post rotablation were rather “loose” and variable. Lack of balloon expansion or inability to pass an I/C catheter were considered “usual practice” for the use of IVL post rotablation, but clear documentation was not available. Although the recommendation as per the calcium algorithm [17], involves the use of I/C imaging for choice of calcium modification tool, it is not widely followed in day-to-day practice. For example, only few (n=19, 10%) out of 190 patients from six centres underwent I/C imaging in the observational, European multicentre study by Aziz et al [12].

Similarly, I/C imaging prior to IVL use was not a mandatory inclusion criterion in the recently published IVL trial (DISRUPT CAD III (NCT03595176)) and only a subset of 100 patients underwent OCT [18]. Even in our patient cohort, we excluded 15% of patients (Figure 2), due to lack of intracoronary imaging.

While our cohort is one of the largest published rotashock and IVL series with the use of intracoronary imaging in all patients, we accept that the calcium plaque/ nodule may be too dense to allow passage of an I/C imaging catheter upfront. Hence, the authors suggest that the use of BCS to assess severity of angiographic calcification may help guide the choice of tool (s) for calcium modification (Figure 3).

Surprisingly, although our rotashock patients had higher angiographic calcium scores (BCS 2/3), they were no more likely to have any of the traditional risk factors for excessive coronary calcification such as DM, CKD etc., in comparison to the IVL alone group. They did however; more frequently have a history of hypercholesterolemia. Statins are known to regress and stabilise coronary plaque (especially fibrous plaque) as well as promote coronary calcification [24-26], and we theorise that the increased calcification in the above group of patients may be explained by statin treatment.

There were no major in-hospital complications such as MI, stroke, death or referral for emergency CABG in the rotashock and IVL groups. Despite the use of two calcium modification tools, no high grade dissections (D-F), were observed in the rotashock group, unlike in DISRUPT CAD III [18]. Ellis 3 perforation and burst IVL balloon were more frequent in the IVL alone group. We speculate that calcium spicules or nodules may be responsible for both these complications. Perhaps the upfront use of rotablation might avoid this. Procedural success rates were unaffected and similar in both groups.

None of the rotashock patients underwent the procedure for under-expanded stents/ISR but more than a third of our IVL alone patients had under-expanded stents and/or ISR. This is similar to data from other observational studies [12,27], and IVL may be preferable to rotablation in these patients who would have historically required the latter [28,29].

Which I/C imaging modality to use? The use of IVUS (as opposed to OCT) to assess I/C calcification can be a limiting factor as it is able to identify only the leading edge of a calcified plaque but may obstruct visualisation of deep calcium [6,19]. Guidelines and consensus documents recommend OCT over IVUS for the identification of calcified coronary plaque [20]. OCT is known to have a higher resolution and accuracy for the detection of calcified plaque compared to IVUS [19-23].

Which patients then would benefit from or require rotashock therapy? The choice of rotablation over IVL as the initial calcium modifying tool may be driven by angiographic calcium severity, inability to pass an I/C catheter and/or the presence of calcium nodules on intracoronary imaging. The choice of IVL after rotablation rather than a second, larger burr or other tool to modify coronary calcium may be influenced by a number of factors including the non-expansion of a balloon post rotablation, lack of calcium fractures, depth of calcium>0.5 mm on I/C imaging or the ease of utilising this modality. A formal cost benefit analysis is needed but currently, financial difference is not an aspect, as both modalities have a similar cost.

The authors suggest rotablation upfront when angiographic calcification BCS is ≥2 and an I/C cannot be passed across the lesion. We also suggest that IVL be utilised after rotablation (rotashock), when there is deep calcification, lack of calcium fracture on I/C imaging or inadequate balloon expansion post rotablation (Figure 3).

There is limited data on rotashock patients and to the best of our knowledge this is one of the first studies to assess the characteristics of the rotashock procedure and patients. Assessment of coronary calcification by a combination of angiographic scoring (BCS) and intracoronary imaging may be required to decide which calcium modifying tool would optimally modify the calcified plaque.

Data from the prospective randomised study (NCT04047368) “Comparison of Coronary Lithoplasty and Rotablation for the Interventional Treatment of Severely Calcified Coronary Stenoses - ROTA.Shock-Trial” will hopefully guide us in relation to the utility of rotashock in calcified lesions.

Our study has some limitations. It is a retrospective study with limited number of patients, however rotashock is a novel combination of two tools and we have combined data from two high volume PCI centres. We included patients with underexpanded stents/ ISR in the IVL group as this was real world data, rather than only de-novo calcified lesions. Details regarding intermediate and long term follow up to compare outcomes between rotashock and IVL alone therapy were also not available.

Rotashock can be performed safely with a low rate of complications for the treatment of heavily calcified coronary plaque. BCS may help guide choice of tool for calcium modification in addition to intracoronary imaging.

We would like to acknowledge Sayeed Karim from the Cardiac audit department for his help with data

1. Jang JJ, Krishnaswami A, Hung YY. Predictive values of Framingham risk and coronary artery calcium scores in the detection of obstructive CAD in patients with normal SPECT. Angiology. 2012; 63: 275-281.

2. Sharma V, Mughal L, Dimitropoulos G, Sheikh A, Griffin M, Moss A, et al. The additive prognostic value of coronary calcium score (CCS) to single photon emission computed tomography myocardial perfusion imaging (SPECT-MPI)-real world data from a single center. J Nucl Cardiol. 2019.

3. Kronmal RA, McClelland RL, Detrano R, Shea S, Lima JA, Cushman M, et al. Risk factors for the progression of coronary artery calcification in asymptomatic subjects: results from the Multi- Ethnic Study of Atherosclerosis (MESA). Circulation. 2007; 115: 2722-2730.

4. Lee MS, Shah N. The Impact and Pathophysiologic Consequences of Coronary Artery Calcium Deposition in Percutaneous Coronary Interventions. J Invasive Cardiol. 2016; 28: 160-167.

5. Moussa I, Ellis SG, Jones M, Kereiakes DJ, McMartin D, Rutherford B, et al. Impact of coronary culprit lesion calcium in patients undergoing paclitaxel-eluting stent implantation (a TAXUS- IV sub study). Am J Cardiol. 2005; 96: 1242-1247.

6. Mintz GS, Popma JJ, Pichard AD, Kent KM, Satler LF, Chuang YC, et al. Patterns of calcification in coronary artery disease. A statistical analysis of intravascular ultrasound and coronary angiography in 1155 lesions. Circulation. 1995; 91: 1959-1965.

7. Sharma V, Abdul F, Haider ST, Din J, Talwar S, O’Kane P, et al. Rotablation in the very elderly - Safer than we think? Cardiovasc Revasc Med. 2020; 22: 36-41.

8. Kassimis G, Raina T, Kontogiannis N, Patri G, Abramik J, Zaphiriou A, et al. How Should We Treat Heavily Calcified Coronary Artery Disease in Contemporary Practice? From Atherectomy to Intravascular Lithotripsy. Cardiovasc Revasc Med. 2019; 20: 1172-1183.

9. Brinton TJ, Ali ZA, Hill JM, Meredith IT, Maehara A, Illindala U, et al. Feasibility of Shockwave Coronary Intravascular Lithotripsy for the Treatment of Calcified Coronary Stenoses. Circulation. 2019; 139: 834-836.

10. Ali ZA, Nef H, Escaned J, Werner N, Banning AP, Hill JM, 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: e008434.

11. Øksnes A, McEntegart M. Intravascular lithotripsy in saphenous vein grafts and graft stent failure: A case series. Catheter Cardiovasc Interv. 2020; 97: 945-950.

12. Aziz A, Bhatia G, Pitt M, Choudhury A, Hailan A, Upadhyaya S, et al. Intravascular lithotripsy in calcified-coronary lesions: A real-world observational, European multicenter study. Catheter Cardiovasc Interv. 2020.

13. Tovar Forero MN, Van Mieghem NM, Daemen J. Stent underexpansion due to heavy coronary calcification resistant to rotational atherectomy: A case for coronary lithoplasty? Catheter Cardiovasc Interv. 2020; 96: 598-600.

14. World Medical A. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013; 310: 2191-2194.

15. von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008; 61: 344-349.

16. Fujino A, Mintz GS, Matsumura M, Lee T, Kim SY, Hoshino M, et al. A new optical coherence tomography-based calcium scoring system to predict stent underexpansion. EuroIntervention. 2018; 13: e2182-e2189.

17. Anja Oksnes, Margaret McEntegart MD P. Intravascular Lithotripsy to Modify Calcified Coronary Artery Disease How to use the Shockwave coronary Rx lithotripsy system. Cardiac Interventions Today. 2020.

18. Hill JM, Kereiakes DJ, Shlofmitz RA, Klein AJ, Riley RF, Price MJ, et al. Intravascular Lithotripsy for Treatment of Severely Calcified Coronary Artery Disease: The Disrupt CAD III Study. J Am Coll Cardiol. 2020; 1: 2635-2646.

19. Sharma SK, Vengrenyuk Y, Kini AS. IVUS, OCT, and Coronary Artery Calcification: Is There a Bone of Contention? JACC Cardiovasc Imaging 2017; 10: 880-882. 

20. Räber L, Mintz GS, Koskinas KC, Johnson TW, Holm NR, Onuma Y, et al. Clinical use of intracoronary imaging. Part 1: guidance and optimization of coronary interventions. An expert consensus document of the European Association of Percutaneous Cardiovascular Interventions. Eur Heart J. 2018; 39: 3281-3300.

21. Yabushita H, Bouma BE, Houser SL, Aretz HT, Jang IK, Schlendorf KH, et al. Characterization of human atherosclerosis by optical coherence tomography. Circulation. 2002; 106: 1640-1645.

22. Mehanna E, Bezerra HG, Prabhu D, Brandt E, Chamié D, Yamamoto H, et al. Volumetric characterization of human coronary calcification by frequency-domain optical coherence tomography. Circ J. 2013; 77: 2334-2340.

23. Wang X, Matsumura M, Mintz GS, Lee T, Zhang W, Cao Y, et al. In Vivo Calcium Detection by Comparing Optical Coherence Tomography, Intravascular Ultrasound, and Angiography. JACC Cardiovasc Imaging. 2017; 10: 869-879.

24. Bittencourt MS, Cerci RJ. Statin effects on atherosclerotic plaques: regression or healing? BMC Med. 2015; 13: 260.

25. Banach M, Serban C, Sahebkar A, Mikhailidis DP, Ursoniu S, Ray KK, et al. Impact of statin therapy on coronary plaque composition: a systematic review and meta-analysis of virtual histology intravascular ultrasound studies. BMC Med. 2015; 13: 229.

26. Puri R, Nicholls SJ, Shao M, Kataoka Y, Uno K, Kapadia SR, et al. Impact of statins on serial coronary calcification during atheroma progression and regression. J Am Coll Cardiol. 2015; 65: 1273-1282.

27. Yeoh J, Cottens D, Cosgrove C, Mallek K, Strange J, Anderson R, et al. Management of stent underexpansion using intravascular lithotripsyDefining the utility of a novel device. Catheter Cardiovasc Interv. 2020.

28. Lee S, Park KW, Kim HS. Stentablation of an underexpanded stent in a heavily calcified lesion using rotational atherectomy. J Cardiovasc Med (Hagerstown). 2012; 13: 284-288.

29. Kobayashi Y, Teirstein P, Linnemeier T, Stone G, Leon M, Moses J. Rotational atherectomy (stentablation) in a lesion with stent underexpansion due to heavily calcified plaque. Catheter Cardiovasc Interv. 2001; 52: 208-211