Coronary artery stenosis or lesions with calcifications are frequently observed in patients undergoing thorough left heart catheterization, especially in patients of advanced age and comorbidities like chronic kidney disease and diabetes. Performing percutaneous intervention in calcified coronary artery lesions always presents a challenge to interventionists because as compared to traditional lesions angioplasty in these lesions are associated with failure of stent deployment, stent mall apposition and thrombosis. In past treatment options for treating calcified lesions were limited but with the advancements in field of coronary interventions now many more options are available in armamentariums of cardiologists to treat calcified lesions [1-5].

Importance of Treating Calcium Before Stent Deployment 

If significant coronary calcium is present, it is particularly important to prep the lesion appropriately before proceeding with any intervention for several reasons. The coronary calcified lesion can impair stent expansion leading to malposition, in addition to that calcified lesion can damage the polymer (delivery vehicle for antiproliferative drug) that can also lead to stent restenosis and thrombosis [6,7].

Different Methods to Treat Calcified Coronary Lesions

Brief review of different methods to treat calcified corner legends are given below.

Use of Balloon Angioplasty

Balloon angioplasty is usually the initial method used by interventionists, especially in setting of mild to moderate calcified lesions with calcification less than 90 degrees. There are different types of balloons available to treat calcified lesions including high pressure non-compliant (NC) balloons, very high-pressure non-compliant balloons (OPN NC balloon, SIS Medical), cutting balloons (Wolverine, Boston Scientific), and scoring balloons (Angio Sculpt, Spectranetics-Philips,NSE Alpha scoring balloon, B Braun). 

The above-mentioned different types of balloons have their specific advantages and disadvantages. NC balloons are easily available and can be inflated at high pressure. Caution should be taken to use NC balloons in severely calcified lesions because it can lead to coronary vessel dissection and perforation. The OPN NC balloon can tolerate even more higher pressure than a conventional NC balloon, due to its double-layer design, there is less risk of coronary dissection or perforation as compared to a conventional NC balloon. Studies have shown ultra-high-pressure balloons are more useful than NC balloons in treating calcified lesions that are difficult to dilate. Cutting balloons (balloon with blades on edges) are another type of balloon that is not frequently used in treatment algorithms of calcified lesions usually have a high complication rate as compared to conventional NC balloons and should be used with caution. On the other hand, scoring balloons (specialized balloons with scoring elements I.e., nitinol struts, to prevent slippage) have shown a better outcome with less risk of coronary dissection [8-13].

Rotational Atherectomy

Rotational atherectomy used a diamond-coated burr that de-calcified or modified the plaque. The device for rotational atherectomy is Rotablator^TM (Boston Scientific, USA) has been approved for treat calcific coronary artery lesions since 1993.

The ROTAXUS is one of the earlier trials in which Rotablator was evaluated. In this trial 240 patients with moderate to severe calcified lesion were randomized into Rotablator plus Taxus stents versus balloon angioplasty plus Taxus stents. The primary endpoint was in-stent late luminal loss. In this trial Rotablator was unable to achieve the primary endpoint and actually showed slightly more in-stent late lumen loss as compared to placebo, but secondary outcomes showed Rotablator has less stent loss and more strategy success rate to treat lesion. The main study population contains both moderate and severe calcified lesions, but further subgroup analysis showed in severe calcified lesions Rotablator was more effective than conventional balloon angioplasty regarding procedure success rate. Another trial PREPARE-CALC trial also showed that rotational atherectomy is associated with less residual stenosis and more procedure success rate [14,15]

Regarding technical aspects rotational atherectomy works on the principle of antegrade differential cutting. It is more useful in lesions that have concentric calcification rather than eccentric. Potential complications include vessel perforation, burr entrapment, and distal embolization with no-reflow phenomena. Each complication can be minimized by different techniques, for example, no-reflow phenomena can be minimized by doing short runs i.e., < 15 sec. with pauses of approximately 30 sec in between two runs. The coronary dissection and perforation can be avoided with proper co-axial engagement with good intubation of the coronary vessel. This device should be used with caution if there is significant vessel tortuosity exists [16,17].

Orbital Atherectomy 

Orbital atherectomy is also another method to treat calcified lesions. It consists of a diamond-coated crown with the capability to do antegrade and retrograde debulking of the plaque. Diamondback 360 (Cardiovascular System, Inc, USA) is the most common orbital atherectomy device that is in use with clinical evidence. The efficacy of orbital atherectomy has been demonstrated in ORBIT I and ORBIT II clinical trials. In both trials, there was a good procedural success rate. Significant coronary artery dissection incidence was approximately 2.3%. Diamondback 360 has a couple of potential advantages over rotational atherectomy including easier setup, less incidence of device entrapment as compared to rotational atherectomy. Regarding technical aspects, it also needs 6 French system and specified Viper wire. Use of orbital atherectomy should be avoided in vessels with severe angulation because of more risks of complications [18-22].

^{Figure 1: Illustration diagram showing different treatment options for calcified coronary lesion.}

^{(Created on biorender.com)}

Use of EXCIMER LASER 

Laser vaporized the calcified plaque by photochemical, photomechanical, and via photothermal methods. The laser used in the percutaneous intervention of calcified lesions had a wavelength of 308 nm. The laser system that is currently mostly in use is Philips CVX-300. An Excimer laser is usually not a first-line modality to treat severely calcified lesions, but it is particularly helpful if the lesion is not able to cross or undilatable. From a technical perspective, the benefits of laser are there is no need to change the wire as we have to do in the case of rotational or orbital atherectomy.  Different kinds of catheters are available with the laser but catheter with size less than 2/3rd of involved artery should be used.   One important thing with the use of laser is very slow advancement of catheter with less than 1 mm/s is advised by experts for good results. The complications of use of Excimer laser are coronary dissection and perforation with variable incidence. To minimize these complications saline solution flush and whenever possible small-caliber catheter should be used [23-26]

Intravascular Coronary Lithotripsy

Intravascular lithotripsy (IVL) is the latest method that has been introduced to treat severely calcified lesions. IVL uses acoustic pressure waves to modify blood vessel calcium get further facilitate stent deployment [27].

Different clinical trials have been done to determine the efficacy of IVL. The initial premarket trial was DISRUPT CAD I. In this trial, 60 patients were enrolled with moderate to severely calcified lesions. The primary endpoint was residual stenosis of less than 50% after the procedure and that was achieved in 95% of the cases, stents were successfully deployed in 100% of the cases. DISRUPT CAD II study was a post-marked trial with more participants. This study also showed clinical success rate of 94.2% with surprisingly 0% angiographic complications including dissection, perforation, abrupt closure and no-reflow. The recently published DISRUPT CAD III was one of the important studies that gave the regulatory approval of this technique. The primary endpoint of the study was a procedural success. In this trial, 431 patients were enrolled with a mean length of the calcified segment was 47.9 mm with a thickness of 0.96 mm.  Effectiveness was demonstrated by doing OCT after lithotripsy and that showed calcium fractures in 67.4% of the lesion. The primary endpoint was the procedural success that was achieved in 92.4% of cases. Regarding technical consideration, IVL can be done via 6 French system. The length of balloon is 12 mm with size varying from 2.5 to 4 mm. Unlike other techniques balloon to artery ratio of 1:1 is used in IVL. The balloon is inflated at low, (4 atmospheric pressure) and then 10 pulses are given at a calcified lesion. By using one balloon a total of 80 pulses can be administered. The advantages of IVL are very less incidence of complications including coronary vessel perforation, dissection, stent thrombosis and no-reflow phenomena and a relatively easy learning curve as compared to other modalities [28-34]

Role of Imaging

Advanced imaging is very important in identifying truly the severity of calcification in coronary lesions because coronary angiograms are less sensitive as compared to advanced imaging modalities like Optical Coherence Tomography (OCT) and intravascular ultrasound (IVUS) in detecting extent and degree of calcium. Imaging is also particularly helpful to rule out stent malapposition [35-38].

Calcified coronary lesions, especially with severe calcification, need special importance and need to be well-prepped for proper stent deployment and apposition. Unsuccessful lesion preparation leads to stent thrombosis and restenosis that can lead to poor procedural outcomes both on a short and long-term basis. Different kinds of plaque modification devices and techniques are in practice ranging from high-pressure balloons to newer addition of intravascular lithotripsy. The general approach is for less calcified lesions high-pressure or modified balloons can be used initially. In case of more severe calcification i.e., more than 90 degrees then based on operator experience or local resources orbital or rotational atherectomy can be used. Excimer laser can also be used but it's more useful in situations when the lesion is not ballooned dilatable and usually in case of severe calcification it is not very effective. Recently intravascular lithotripsy also has been approved to treat severely calcified lesions with great results demonstrated in initial trials.

Nonetheless one device cannot treat all types of calcified lesions and selection of device showed based on specific lesion characteristics, operator experience and local resources. Further randomized clinical trial and long-term data are needed to further understand the pros and cons of each device.

1. Madhavan, M.V. et al. “Coronary Artery Calcification: Pathogenesis and Prognostic Implications.” Journal of the American College of Cardiology, vol. 63, 2014, pp. 1703–1714. https://doi.org/10.1016/j.jacc.2014.01.017.

2. Mintz, G.S. et al. “Patterns of Calcification in Coronary Artery Disease: A Statistical Analysis of Intravascular Ultrasound and Coronary Angiography in 1155 Lesions.” Circulation, vol. 91, 1995, pp. 1959–1965. https://doi.org/10.1161/01.cir.91.7.1959.

3. Généreux, P. et al. “Ischemic Outcomes after Coronary Intervention of Calcified Vessels in Acute Coronary Syndromes.” Journal of the American College of Cardiology, vol. 63, 2014, pp. 1845–1854. https://doi.org/10.1016/j.jacc.2014.01.034.

4. Onuma, Y. et al. “Efficacy of Everolimus-Eluting Stent Implantation in Patients with Calcified Coronary Culprit Lesions.” Catheterization and Cardiovascular Interventions, vol. 76, 2010, pp. 634–642. https://doi.org/10.1002/ccd.22541.

5. Chambers, J.W. et al. “Pivotal Trial to Evaluate the Safety and Efficacy of the Orbital Atherectomy System in Severely Calcified Coronary Lesions (ORBIT II).” JACC: Cardiovascular Interventions, vol. 7, 2014, pp. 510–518. https://doi.org/10.1016/j.jcin.2014.01.158.

6. Bourantas, C.V. et al. “Prognostic Implications of Coronary Calcification in Patients with Obstructive Coronary Artery Disease.” Heart, vol. 100, 2014, pp. 1158–1164. https://doi.org/10.1136/heartjnl-2013-305180.

7. Généreux, P. et al. “Two-Year Outcomes after Percutaneous Coronary Intervention of Calcified Lesions with Drug-Eluting Stents.” International Journal of Cardiology, vol. 231, 2017, pp. 61–67. https://doi.org/10.1016/j.ijcard.2016.12.150.

8. Barath, P. et al. “Cutting Balloon: A Novel Approach to Percutaneous Angioplasty.” American Journal of Cardiology, vol. 68, 1991, pp. 1249–1252. https://doi.org/10.1016/0002-9149(91)90207-2.

9. Okura, H. et al. “Restenosis Reduction by Cutting Balloon Evaluation.” Catheterization and Cardiovascular Interventions, vol. 57, 2002, pp. 429–436. https://doi.org/10.1002/ccd.10344.

10. Mauri, L. et al. “Cutting Balloon Angioplasty for the Prevention of Restenosis.” American Journal of Cardiology, vol. 90, 2002, pp. 1079–1083. https://doi.org/10.1016/S0002-9149(02)02773-X.

11. Neumann, F.J. et al. “2018 ESC/EACTS Guidelines on Myocardial Revascularization.” European Heart Journal, vol. 40, 2019, pp. 87–165. https://doi.org/10.1093/eurheartj/ehy394.

12. Patel, M.R. et al. “2016 Appropriate Use Criteria for Coronary Revascularization in Acute Coronary Syndromes.” Journal of the American College of Cardiology, vol. 69, 2017, pp. 570–591. https://doi.org/10.1007/s12350-017-0780-8.

13. Sadamatsu, K. et al. “Comparison of Pre-Dilation with a Non-Compliant Balloon versus a Dual Wire Scoring Balloon.” World Journal of Cardiovascular Diseases, vol. 3, 2013, pp. 395–400. https://doi.org/10.4236/wjcd.2013.36061.

14. Abdel-Wahab, M. et al. “High-Speed Rotational Atherectomy before Paclitaxel-Eluting Stent Implantation.” JACC: Cardiovascular Interventions, vol. 6, 2013, pp. 10–19. https://doi.org/10.1016/j.jcin.2013.01.003.

15. Abdel-Wahab, M. et al. “High-Speed Rotational Atherectomy versus Modified Balloons before Drug-Eluting Stent Implantation (PREPARE-CALC).” Circulation: Cardiovascular Interventions, vol. 11, 2018, e007415. https://doi.org/10.1161/CIRCINTERVENTIONS.118.007415.

16. Sulimov, D.S. et al. “Stuck Rotablator: The Nightmare of Rotational Atherectomy.” EuroIntervention, vol. 9, 2013, pp. 251–258.

17. Sharma, S.K. et al. “North American Expert Review of Rotational Atherectomy.” Circulation: Cardiovascular Interventions, vol. 12, 2019, e007448.

18. Barbato, E. et al. “European Expert Consensus on Rotational Atherectomy.” EuroIntervention, vol. 11, 2015, pp. 30–36.

19. Parikh, K. et al. “Safety and Feasibility of Orbital Atherectomy: The ORBIT I Trial.” Catheterization and Cardiovascular Interventions, vol. 81, 2013, pp. 1134–1139.

20. Chambers, J.W. et al. “Pivotal Trial Evaluating Orbital Atherectomy (ORBIT II).” JACC: Cardiovascular Interventions, vol. 7, 2014, pp. 510–518.

21. Lee, M. et al. “Three-Year Results of the ORBIT II Trial.” Cardiovascular Revascularization Medicine, vol. 18, 2017, pp. 261–264.

22. Sharma, S. et al. “Treatment of Severely Calcified Lesions with the Micro Crown System: COAST Trial One-Year Results.” JACC: Cardiovascular Interventions, vol. 3, 2017, pp. S1–S2.

23. Appelman, Y.E. et al. “Randomized Trial of Excimer Laser Angioplasty versus Balloon Angioplasty.” Lancet, vol. 347, 1996, pp. 79–84.

24. Fernandez, J.P. et al. “Excimer Coronary Laser Atherectomy Alone or with Rotational Atherectomy.” EuroIntervention, vol. 9, 2013, pp. 243–250.

25. Mohandes, M. et al. “Excimer Laser in PCI of Uncrossable Occlusions.” Cardiovascular Revascularization Medicine, August 2019. https://doi.org/10.1016/j.carrev.2019.08.022.

26. Lee, T. et al. “The Effectiveness of Excimer Laser Angioplasty to Treat Coronary In-Stent Restenosis with Peri-Stent Calcium.” EuroIntervention, vol. 15, 2019, pp. e279–e288.

27. Hill, J.M. et al. “Intravascular Lithotripsy for Treatment of Severely Calcified Coronary Artery Disease: The DISRUPT CAD III Study.” Journal of the American College of Cardiology, 2020. https://doi.org/10.1016/j.jacc.2020.01.015.

28. Serruys, P.W., Y. Katagiri, and Y. Onuma. “Shaking and Breaking Calcified Plaque: Lithoplasty, a Breakthrough in Interventional Armamentarium?” JACC: Cardiovascular Imaging, vol. 10, 2017, pp. 907–911.

29. Rodriguez Costoya, I. et al. “Coronary Lithoplasty: Initial Experience in Coronary Calcified Lesions.” Revista Española de Cardiología, vol. 72, 2019, pp. 788–790.

30. Brinton, T.J. et al. “Feasibility of Shockwave Coronary Intravascular Lithotripsy for Calcified Coronary Stenoses.” Circulation, vol. 139, 2019, pp. 834–836. https://doi.org/10.1161/CIRCULATIONAHA.119.039153.

31. Ali, Z.A. et al. “Safety and Effectiveness of Coronary Intravascular Lithotripsy for Severely Calcified Coronary Stenoses: The Disrupt CAD II Study.” Circulation: Cardiovascular Interventions, vol. 12, 2019, e008434.

32. Wong, B. et al. “Shockwave Intravascular Lithotripsy for Calcified Coronary Lesions: First Real-World Experience.” Journal of Invasive Cardiology, vol. 31, 2019, pp. 46–48.

33. Tovar Forero, M.N., J. Wilschut, N.M. Van Mieghem, and J. Daemen. “Coronary Lithoplasty: A Novel Treatment for Stent Underexpansion.” European Heart Journal, vol. 40, 2019, p. 221.

34. Watkins, S. et al. “Intravascular Lithotripsy to Treat a Severely Underexpanded Coronary Stent.” EuroIntervention, vol. 15, 2019, pp. 124–125.

35. Bourantas, C.V. et al. “Prognostic Implications of Severe Coronary Calcification in Patients Undergoing Coronary Artery Bypass Surgery: Analysis of the SYNTAX Study.” Catheterization and Cardiovascular Interventions, vol. 85, 2015, pp. 199–206. https://doi.org/10.1002/ccd.25545.

36. Sharma, S.K., Y. Vengrenyuk, and A.S. Kini. “IVUS, OCT, and Coronary Artery Calcification: Is There a Bone of Contention?” JACC: Cardiovascular Imaging, vol. 10, 2017, pp. 880–882.

37. Fujino, A. et al. “A New Optical Coherence Tomography-Based Calcium Scoring System to Predict Stent Underexpansion.” EuroIntervention, vol. 13, 2018, pp. e2182–e2189.

38. Zhang, M. et al. “IVUS Predictors of Stent Expansion in Severely Calcified Lesions.” Journal of the American College of Cardiology, vol. 74, 2019, p. B51.