Authors: Nagendra Boopathy Senguttavan, Venkatakrishnan Ramakumar, Nitish Naik, Annapoorna Kini, Samin K. Sharma
Categories: Editorial, Coronary artery disease, Coronary calcification, Percutaneous coronary intervention
Source: Indian Heart Journal
Authors: Nagendra Boopathy Senguttavan, Venkatakrishnan Ramakumar, Nitish Naik, Annapoorna Kini, Samin K. Sharma
Coronary artery calcification (CAC) has emerged as a distinct subset of coronary artery disease. CAC is common, and can be detected in up to 90 % of men and in greater than 67 % of women above the age of 70 years by CT coronary angiography.^1^ Additionally, up to one-fourth of patients undergoing percutaneous coronary interventions (PCI) demonstrate moderate to severe calcification.^2^^,^^3^ Advanced age, chronic kidney disease (CKD) and diabetes mellitus have been shown to predispose to increased intimal or medial calcification.^2^ In addition, several traditional risk factors for atherosclerotic disease like cigarette smoking, male sex and dyslipidaemia may predispose to intimal calcification in particular.^2^ Therefore, the incidence of CAC appears to be on the rise.^2^ Interestingly, recent studies have also shown very vigorous exercise to result in enhanced CAC burden in middle aged athletes.^4^
CAC may hold several physiological and pathological implications. The presence of CAC results in physiological changes such as decreased arterial compliance, and reduced myocardial perfusion.^5^ The presence of CAC is considered highly specific for the atherosclerotic disease process, and is also strongly associated with greater plaque burden and lesion complexity.^6^ Therefore, while previously considered a marker for stability within atherosclerotic cardiovascular disease (ASCVD), recent insights have shown such dystrophic calcification to be a part of a broader systemic inflammatory process mediated by inflammatory mediators.^6^ Accordingly, CAC has been shown to portend a higher risk for major adverse cardiac events (MACE) not only in patients undergoing revascularisation but also in the general population.6, 7, 8, 9 Pooled data from HORIZONS-AMI and ACUITY trials comprising of 6855 patients undergoing PCI for acute coronary syndrome (ACS) revealed higher 1-year MACE rates in those with moderately or severely calcified lesions, with multivariate analysis demonstrating severe calcium to result in 62 % higher risk of 1-year definite stent thrombosis (p = 0.007).^10^ In the MACE-Trial (Multi-centre Prospective Study to Evaluate Outcomes of Moderate to Severely Calcified Coronary Lesions), which included patients undergoing DES implantation, those with severe calcification had a 1-year MACE rate of 24 % (p < 0.001).^11^ A large multi-ethnic registry reported 63 % higher 1-year MACE rates (aHR, 1.63; 95 % CI, 1.42, 1.86, p < 0.001) in patients with moderate or severe CAC.^7^ Similarly, in a large meta-analysis of patients enrolled from the BIOFLOW II, IV and V trials, moderate or higher calcification resulted in significantly higher target vessel myocardial infarctions (aHR, 1.66; 95 % CI, 1.03–2.68; p = 0.037).^12^ Furthermore, the presence of calcium may also indicate unfavourable long term survival outcomes. The 10-year follow-up of patients from the SYNTAXES study demonstrated that those with heavily calcified lesions had a higher all-cause mortality rate than those without, an effect that extended to patients who underwent CABG as well.^13^
Additionally, it is well known that CAC also poses major challenges during intervention. Calcification results in technical difficulties in performing PCI, particularly with equipment delivery and stent expansion, with possible poor immediate and long-term outcomes. Furthermore, complications during PCI, such as perforation are increased in such patients with CAC.14, 15, 16 The above features thus necessitate the distinction of CAC as a unique pathobiological and interventional entity.
ICA has been among the earliest modalities to detect CAC. Severe coronary calcification on ICA is defined as vessel calcification seen on both sides of the vessel (the classical “tram-track” appearance), or is discernible without the need for cardiac motion or contrast injection. Moderate calcification is defined as opacities discernible only with cardiac motion. Mild calcification cannot be discerned on ICA. Correspondingly, ICA has demonstrated low sensitivity for CAC. Two early studies comparing ICA to Intravascular ultrasound (IVUS) showed ICA to have a modest sensitivity of 38–40 %.^17^^,^^18^ Another more recent study revealed ICA to have a sensitivity of 40.2 %.^19^ Therefore, intracoronary imaging techniques have superseded ICA in the setting of CAC definition and detection.
Intravascular imaging (IVI) represents a more informative diagnostic method for CAC. Several studies have shown IVUS and optical coherence tomography (OCT) to be superior in sensitivity to ICA, with a sensitivity of 73–82 % in comparison with histology.^17^^,^^19^ However, IVUS and OCT also offer additional lesional information that may be crucial for decisions regarding strategy and optimization of PCI. These include characteristics such as the circumferential arc of calcium, thickness of calcification (Fig. 1, Part A and B), location of calcium (Fig. 2), and others such as the longitudinal length of calcium and the concomitant presence of a large necrotic core. IVI has also helped define specific morphologies of calcification such as calcific nodules (a protruding eccentric stalactite like mass of calcium with an underlying calcific plate, Fig. 3) and circumferential 360° calcium (Fig. 4), which may have important prognostic connotations.^20^^,^^21^ While IVUS and OCT demonstrate equivalent efficacy in defining the length and the arc of calcium, OCT is superior in accurately defining the thickness of calcium, owing to sound waves of IVUS being attenuated by calcific arcs. On the contrary, IVUS is superior to assess large vessels, ostial lesions, and is the preferred modality in patients with CKD.^22^Fig. 1A and B. A severely calcified lesion seen on OCT and IVUS, respectively. Calcium plate thickness (visible on OCT, asterisk, yellow double-sided arrow) and calcium arc (visible on both modalities, yellow curved arrows) are discernible, aiding lesion assessment and planning. (representative images). © 2018–2025 Icahn School of Medicine at Mount Sinai. All Rights Reserved.Fig. 1Fig. 2Coronary calcium can be classified as superficial (calcium at the intimal–lumen interface, or closer to the lumen and away from the adventitia), and deep (calcium at the media-adventitia border or closer to the adventitia and away from the lumen). © 2018–2025 Icahn School of Medicine at Mount Sinai. All Rights Reserved.Fig. 2Fig. 3Calcific nodule seen on IVUS (part A, blue arrows) and OCT (Part B, asterisk). Multiple irregular calcific protuberances extending into the lumen. (representative images).© 2018–2025 Icahn School of Medicine at Mount Sinai. All Rights Reserved.Fig. 3Fig. 4360° calcium arc seen in a patient with a severe calcified lesion. © 2018–2025 Icahn School of Medicine at Mount Sinai. All Rights Reserved.Fig. 4
The use of IVI to assist PCI has been shown to result in better short-term and long-term outcomes including all-cause mortality.23, 24, 25, 26 Aside from the potential benefits of IVI in PCI overall, it appears that IVI may be of particular benefit in calcified lesions. An OCT-based scoring system to predict risk of stent under-expansion was developed by Fujino et al comprising of the calcium arc, calcium thickness and length of calcification.^27^ The presence of a calcium arc >180°, thickness of >0.5 mm and a calcium length of >5 mm was associated with significant risk of stent under-expansion (96 % versus 78 %, p < 0.01).^27^ Another IVUS-based scoring system by Zhang et al suggested that in angiographically detected CAC with a calcium arc of >270°, the presence of a calcific nodule, circumferential 360° calcium, vessel diameter <3.5 mm and a three quadrant calcium length of >5 mm predicted significant risk of stent under-expansion.^21^ Also, evidence has since emerged suggesting strong correlation between IVUS and histopathological findings, validating the accuracy of IVI in calcific lesions.^24^ Furthermore, imaging performed after angioplasty techniques to treat calcified lesions can help determine adequacy of lesion preparation.^28^ The creation of calcium fractures (Fig. 5) in calcific lesions has been shown to facilitate PCI and produce favourable outcomes.^28^^,^^29^ Recent studies have identified factors determining ease of fracture creation, particularly, patterns of calcification and calcium thickness. In a small study by Maejino et al on patients with CAC with a rotational atherectomy based strategy, segments with calcium cracks after angioplasty had a larger median calcium arc (360°, IQR, 246–360° vs. 147°, IQR, 118–199°, p < 0.001) and a thinner calcium thickness (0.53 ± 0.28 vs. 1.02 ± 0.42 mm, p < 0.001) than those without.^30^ In a larger study by Fujino et al, calcium fracture after balloon pre-dilatation alone occurred in lesions with greater maximum calcium angle (295° vs. 109°; p < 0.01) and smaller minimum calcium thickness (0.20 mm vs. 0.45 mm; p < 0.01).^29^ As seen in both studies, careful assessment of lesion morphology on IVI is important for adequate lesion preparation and to yield durable results. IVI has therefore been given a class 2a recommendation by the 2021 American College of Cardiology guidelines for procedural guidance in the setting on complex disease to reduce ischemic events.^31^ Therefore, in the setting of CAC, the aforementioned utility of IVI in detailing lesions mandates an even lower threshold for IVI, and an “image-first” strategy may be most prudent.Fig. 5Densely calcified lesion segments seen on OCT (asterisk). Multiple fractures (white arrowheads) are seen post successful intravascular lithotripsy (IVL) which help facilitate subsequent lesion expansion. © 2018–2025 Icahn School of Medicine at Mount Sinai. All Rights Reserved.Fig. 5
Sufficient and optimal lesion preparation is paramount in PCI of calcific lesions. Routine pre-dilatation with non-compliant balloons may often be inadequate for preparation, particularly in the presence of high risk features. Specialised techniques, are therefore recommended. Several strategies have hitherto been reported.32, 33, 34, 35 We propose an algorithmic approach based on imaging features, and equipment crossability (Fig. 6.). Techniques to modify calcium can be classified into balloon angioplasty-based techniques and debulking techniques.Fig. 6Proposed algorithm for management of severely calcified lesions.CABG: Coronary Artery Bypass Grafting, CB: Cutting Balloon, NC: Non-compliant Balloon, HPB: High-Pressure twin-layered non-compliant Balloon, SB: Scoring Balloon.∗Represents high risk calcific features on IVUS/OCT, namely, presence of calcium thickness >0.5 mm, Length >5 mm or calcium arc>180°, presence of a calcific nodule.^&^Represents IVI catheter uncrossable lesions. In such cases balloon angioplasty or rotational atherectomy are to be performed and IVI catheter passage is attempted subsequently.^CABG can be considered if appropriate (left main disease, triple vessel disease, high complexity disease, other cardiac surgery planned)^#^Represents off label usage.Fig. 6Fig. 7Special situations with calcification.Choice of device to be decided by several determinants including balloon crossability, calcium arc, depth, length, nodularity.CB= Cutting balloon ELCA = Excimer laser coronary atherectomy HPB= High-pressure balloon IVL= Intravascular lithotripsy OA= Orbital atherectomy RA = Rotational atherectomy SB= Scoring balloon.#Represents off-label use. ELCA in in-stent restenosis may need ”contrast lasing”, i.e. usage of higher concentrations of contrast to deliver greater energy. RA in in-stent restenosis is known as “stent-ablation”, i.e. ablation of firm neointimal or atherosclerotic tissue within the stent.^If bias is favourable. Rotational atherectomy in a nodular lesion may require the use of ROTAWire Extra Support ™.^$^ Atherectomy can be performed in bifurcation lesions if wire removal from side branch is acceptable. “Half-way rota" can also be performed-which is burring of the main vessel along and stopping before the main branch-side branch confluence.Fig. 7
The cutting balloon (CB) is a semi-compliant balloon with 3–4 microsurgical blades mounted longitudinally.^36^ They are available in 3 lengths (6 mm, 10 mm and 15 mm) and diameters (2.25 mm, 2.5 mm, 2.75 mm and 3.0 mm). The desired resultant effect is a focussed radial force producing shallow endovascular radial incisions, exposing more elastic tissue and reducing recoil, thereby improving vessel compliance and expansion.^37^ An IVUS-based study showed significantly improved acute luminal gains in patients with CB in comparison to conventional plain old balloon angioplasty (POBA).^37^ Additionally these blades also prevent slippage, which may be of particular importance in in-stent restenosis (ISR) and in aorto-ostial lesions.^38^^,^^39^ Earlier studies not restricted to calcified coronary lesions yielded mixed results. A moderate sized study comparing CB to POBA in type B/C lesion in vessels < 3 mm diameter showed significantly reduced restenosis rates at 3 months, with similar post-procedural luminal gains and complication rates.^40^ However, larger studies comparing CB with conventional BA demonstrated poor results with high complication rates, particularly the Cutting Balloon Global Randomized Trial.^41^ Acute procedural success was not different (31.4 % vs 30,4 %; p = 0.75). However, complication rates were higher, namely five coronary perforations, which occurred in the CB arm only (0.8 % vs 0 %, p = 0.03). However, in the setting of calcified lesions, CB may be particularly useful. A small retrospective analysis by Karvouni et al demonstrated better acute luminal gain (ALG) in low pressure dilatation with CB in comparison to BA.^42^ In the REDUCE III randomised study comprising of 521 patients who underwent PCI with bare metal stents, CB demonstrated significantly higher minimal luminal diameters (2.65 ± 0.40 mm vs 2.52 ± 0.4 mm, p < 0.01) than BA.^43^ Another recent retrospective study analysed clinical outcomes between CB, POBA and RA in 737 patients with angiographically severe calcific lesions undergoing PCI with DES.^44^ Notably, 74.4 % patients underwent IVUS guided optimization and 46.6 % patients underwent second generation DES. The study showed similar rates of all-cause mortality, non-Q-wave MI and TLR at 12 months.^44^ However, in the recent ROTACUT trial, CB after RA did not significantly improve minimum stent area compared to a rotational atherectomy (RA) followed by non-compliant POBA (6.7 ± 1.7 mm2 versus 6.9 ± 1.8 mm2; p = 0.685).^45^ This was possibly due to diminished additive value of the CB after rotational atherectomy. Interestingly, recent data has supported higher pressure dilatations and less conservative use of the CB. In the COPS trial, dilation of up to 18–20 atm with the CB yielded better minimal lesion areas after predilatation (8.2 mm^2^ vs 7.3 mm^2^; p = 0.035) in comparison to NC balloon dilatation, with similar 1-year clinical events.^46^ A total of 2 perforations were noted possibly due to oversizing and improper lesion selection.^46^ These findings could herald expanded usage of the CB with greater procedural success.
**Optimal ** *Selection of a CB 0.*5mm smaller than that of the predicted stent size, or 0.25mm smaller than the average lumen diameter of the distal reference site is recommended by us. The CB must be inflated slowly at 2atm. every second. Once nominal pressure is reached, cine-angiographic expansion is assessed, preferably in two orthogonal planes to ensure near circular expansion. If poor expansion is seen, higher pressure dilatations may be performed (to a maximum of 18atm). To attain best results, the balloon must be removed out of the vessel and rotated inside the guiding catheter and reintroduced after rotating by 60-90° to ensure a different site of blade attachment within the artery and CB dilatation is repeated. A check angiogram post CB usage is strongly recommended to help identify perforations, if any.
Risks of complications with CB prompted the development of the scoring balloon (SB). This is a semi-compliant balloon with 3–4 rectangular nitinol wires wrapped helically around the balloon. This offers an added mechanism of calcific plaque modification over and above POBA. Early studies showed promising results. De Ribamar Costa Jr et al reported IVUS guided PCI following SB to produce better stent expansion in comparison with POBA based PCI or direct stenting in de novo lesions.^47^ In another study by Jujo et al, better ALG was seen on OCT after predilatation with SB in comparison to semi-compliant balloon predilatation.^48^ Another study which included complex and calcific lesions, found better luminal area ratios (0.71 vs. 0.86; p < 0.001) and more uniform stent expansion (p < 0.001) in patients undergoing Biovascular scaffold (BVS) PCI.^49^ Theoretically, the SB offers a more controlled focussed force, reducing dissection risks, while also reducing the delivery profile in comparison to the CB. However, a comparative study between the Lacrosse**^TM^** SB and the Wolverine**^TM^** CB has contested the theoretical advantages of SB over CB, with better deliverability in CB (90.8 % versus 79.5 %, p = 0.006), and similar luminal gains.^50^ Further head-to-head studies to delineate the veracity of the potential advantages are needed.
**Optimal ** Technique similar to that employed for CB is recommended. A slow and controlled inflation is preferred. A second inflation similar to CB to obtain maximal gain may be performed.
A recent addition to the interventional toolbox is the dual-layered “twin-wall” high pressure balloon (HPB) such as the OPN NC balloon (Sis Medical AG, Switzerland). These are dual layered balloons resulting in uniform expansion while delivering high dilatation pressures (a rated burst pressure of up to 35 atm, factory tested up to 45 atm).^51^ Initial case series yielded good results in failed pre-dilatation, in-stent restenosis and under-expanded stents when inflations of up to 35–40 atm were performed.^52^^,^^53^ A larger study of 91 patients undergoing high pressure dilatation with the HPB after failed pre-dilatation revealed significantly improved ALG (41.1 ± 15.8 % versus 20.2 ± 14.9 %, p < 0.001). In another study of 71 patients undergoing pre- and post-dilatation, the OPN balloon demonstrated a good safety profile.^54^ The ISAR-CALC open-label randomised study comprising of 74 patients showed that in patients with unsuccessful pre-dilatation with a non-compliant balloon, the HPB balloon increased the minimum lumen diameter (2.83 ± 0.34 mm vs 2.65 ± 0.36 mm; p = 0.03) and reduced the residual diameter stenosis (11.6 ± 4.8 % vs 14.4 ± 5.6 %; p = 0.02) to a greater extent than the CB.^55^ The OPN NC balloon device subsequently received the FDA 510(k) clearance in 2023. However, edge-dissections and shaft breaks have been reported.^54^^,^^56^ The HPB has also been used in complex hybrid procedures where more than one calcium-modifying strategy may be used, and in special scenarios such as deep calcium and nodular calcium.^57^^,^^58^
Optimal technique: *Use of a non-hydrophilic wire is recommended. Under-sizing of the balloon by 0.*5mm for pre-dilatation for initial calcium fracture followed by near 1 non-complaint balloon usage to further expand the lesion is recommended. In the post-dilatation group, a 1 sized balloon in a non-tortuous straight segment is recommended. Imaging is strongly recommended 1. pressures greater than the rated burst pressure are employed 2. high pressure balloons greater than 3mm are to be used 3. 1 dilatations in a tortuous segment are performed. Backup equipment such as appropriate sized covered stents are to be ensured. A buddy wire prior to balloon removal may be useful after multiple high pressure dilatations to prevent wire loss due to balloon adherence to guidewire.
The need for easily deliverable, atraumatic balloon-based technologies heralded the advent of the most recent addition to the toolbox in calcified lesions, namely, IVL. This is a single-layered 12 mm semi-compliant balloon with spark gap-based internal emitters located 6 mm apart from each other. The balloon is connected to a dual port hub, one hub connected to the inflation device containing a mixture of contrast and saline (3:2 ratio), and another connected to the pulse generator via a connector cable.^59^ The balloon sizing is performed in a 1 fashion with the target vessel. The balloon is inflated to 4 atm to aid uniform and adequate apposition with the vessel wall. When activated, electrical energy delivered by the emitters is used to convert the saline contrast mixture into vapour which generates high amplitude ultrasonic pressure waves. These waves reach up to 50 atm pressure and preferentially affect hard tissue. A total of 80 pulses can be delivered, with 10 pulses per cycle. The resultant effect is the production of multiple circumferential microfractures of calcific regions.^59^ The new Shockwave C^2+^ IVL catheter has been recently introduced, which can produce up to 120 pulses and therefore be used to treat longer lesions and denser calcium.
IVL may be particularly useful considering its favourable learning curve and atraumatic nature. The technology was tested in the first-in-man DISRUPT CAD I study, which was a multi-centre single arm observational study.^60^ In included patients, who were those with angiographically severe calcified lesions with lesion length <32 mm, the technology had shown 98 % procedural success and 100 % stent delivery, and a mean ALG of 1.7 ± 0.6 mm. 30-day MACE was reported to be 5 %, all of which were from non-Q-wave MI.^60^ The safety and efficacy of IVL was further tested in the DISRUPT CAD II study.^61^ Amongst 120 patients with calcific lesions, IVL catheter delivery was successful in 100 % patients. The mean angiographic ALG seen was 0.83 ± 0.47 mm. An OCT based sub-study of 47 patients demonstrated calcium fractures in 78.7 % of lesions.^61^ Importantly, the primary safety endpoint of 30-day MACE was seen in 5.8 % patients, all of whom were non-Q-wave MI.^61^ Furthermore, data from the SHOCK-India registry showed good efficacy for an OCT-guided IVL strategy, with 88 % patients achieving calcium fractures after IVL. ALG achieved in this study was 1.85 ± 1.22 mm compared to pre-stent diameters.^62^ Similarly, an OCT-based study revealed good efficacy of IVL in the presence of calcium nodules (fracture rate 0f 78.7 % vs 65.2 %, p = 0.07).^63^ The DISRUPT CAD III study was a multicentre single arm study to assess the short term clinical outcomes after IVL.^64^ In 431 patients with calcified lesions, the primary efficacy end point, which was procedural success (defined as successful stenting with <50 % residual stenosis and no in-hospital MACE) was seen in 92.4 % patients. The primary safety end point (defined as freedom from MACE at 30 days), was seen in 92.2 % patients, exceeding the pre-specified performance goal of 84.4 % (p < 0.0001).^64^ The OCT sub-study had also shown fractures in 67.4 % of patients, with fractures often being multiplanar. Interestingly, stent areas were similar between those with and without visible fractures on OCT. This could probably be due to some fractures being out of plane, or too small for the resolution of OCT.^64^ Long term MACE data with IVL has since emerged. In the 1-year follow study of patients in DISRUPT CAD III, reported MACE rates at 13.8 % at 1 year (which included cardiac death of 1.1 % and MI of 10.5 %) making IVL a safe and effective modality for use in CAC.^65^
Complications with IVL seem largely due to non-Q-wave-MI. Several early studies had shown low rates of serious dissections and no-reflow.^60^^,^^61^^,^^64^ Interestingly, IVL may result in capture and ectopic activity, referred to as “shocktopics”. This results from electromechanical coupling due to activation of the stretch receptors that activate the conduction system. Such incidence of shocktopics was reported in up to 41.1 % patients in the DISRUPT CAD III study.^64^ The major risk factor for the phenomenon appears to be low patient heart rate, with rates less than 60/min being at risk due to pulses being delivered at 1 Hz. Fortunately, however, low energy output of IVL curtails the risks of malignant ventricular arrhythmias. Usual patterns remain restricted to single atrial capture, single ventricular capture and ventricular capture longer than 1 beat.^59^^,^^64^
**Optimal ** The optimal approach to device usage is treating IVL as a device that fractures calcium rather than a balloon that performs angioplasty. Therefore adequate bed preparation is paramount. We recommend 1 balloon sizing with the segment of interest to ensure optimal contact and delivery of energy. However, a balloon sized to distal vessel may be useful in case of multiple lesions where the proximal lesion is severely stenosed. Ideally a heart rate of above 60 beats per minute is safer to reduce the risk of shocktopics. Inflation up to 4atm before delivery and 6atm after delivery of pulses to test adequate expansibility. If found inadequate on balloon expansion or IVI, repeat pulses are required. In the setting of size discrepancy between the proximal and distal segments of long lesions, different-sized balloons for IVL may be required. Longer intervening rest periods between cycles are recommended in patients with borderline hemodynamics. If adequate contact is ensured, it is well suited as an up-front agent in deep calcium.
Plaque modification of moderate to severely calcified lesions can be performed by using a rapidly rotating diamond burr, that reduces calcified tissue into small particles when advanced. This is performed by passing a diamond encrusted burr advanced over a specialised 0.009” wire (called the RotaWire**™**) via a helical driveshaft. The burr rotates at speeds of 140,000 to 220,000 rpm, generating debris of size <10 μm, which are subsequently cleared by the reticuloendothelial system. The system preferentially acts on inelastic fibro-calcified tissue through a combination of differential cutting and orthogonal displacement of friction.^38^ Current usage configurations have been shaped by data accrued over a large number of years. Initial studies revealed higher TLR with RA in comparison to BA (42 % vs 32 %, p = 0.01). This initiated the need to explore less aggressive strategies to limit complications.66, 67, 68 In the STRATAS and CARAT trials, patients were randomised to a smaller plaque modifying strategy versus larger burr sizing strategy.^69^^,^^70^ In both studies lower complications rates were seen with the less aggressive strategy, with similar 6-month MACE rates. Similarly, in the SARS trial, lower burr speeds were shown to lower complication rates in RA.^71^ Currently, RA is used primarily as a means to modify plaques to facilitate subsequent successful balloon angioplasty. Such a shift has facilitated the use of smaller equipment, improving safety and potentially yielding better outcomes.^72^ Notably, procedural success and safety may also depend on operator expertise and centre volume. Data from the National Cardiovascular data registry CathPCI registry revealed a small but significant mortality difference between those undergoing RA in high vs low volume centres.^73^ Another large observational study from Japan reported nearly three times higher complication rates requiring bailout procedures in low volume centres compared to those with large volumes.^74^
Trials examining the efficacy of RA in successful PCI have yielded mixed results. In the initial COBRA trial, 502 patients undergoing PCI for calcific lesions were randomised to RA versus BA.^67^ The study revealed no significant difference between the two methods with respect to 6-month TLR and restenosis rates. In the ROTAXUS trial, 240 patients undergoing PCI with paclitaxel DES were randomised to RA versus no RA.^75^ Higher procedural success was seen in the RA group (92.5 % versus 83.3 %, P = 0.03) with no increase in complication rates. Higher cross over rates to the RA group were also seen (12.5 % vs 4.2 %, p = 0.02).^75^ However, despite higher ALG initially (1.56 ± 0.43 versus 1.44 ± 0.49 mm, P < 0.01), higher in-stent late-lumen-loss was seen in the RA group (0.44 ± 0.58 versus 0.31 ± 0.52, P = 0.04). Additionally, although not powered to assess clinical outcomes, RA demonstrated similar clinical outcomes at 2 years versus BA.
The recent PREPARE-CALC trial randomised 200 patients with severe calcific disease (defined as radiopacities noted without cardiac motion before contrast injection generally compromising both sides of the arterial lumen) with Orsiro Sirolimus DES to RA versus CB or SB.^76^ Patients undergoing RA had higher procedural success rates (98 % versus 81 %, p < 0.001), whereas mean in-stent late-lumen loss at 9 months was slightly higher in the RA group (0.22 ± 0.40 mm vs 0.16 ± 0.39 mm, p = 0.21, p = 0.02 for noninferiority). Target lesion revascularisation (7 % versus 2 %; P = 0.17) was not significantly different.^76^ RA currently is a widely used, efficacious device for moderate and severe calcium, particularly when crossability is difficult or doubtful.
**Optimal ** *The optimal burr-to-artery size is 0.4-0.6. The use of long sheaths for better stability is strongly recommended. 6 French guiding catheters are appropriate for up to 1.*5mm *burrs. A 1.*75mm burr necessitates 7 French catheters. A balloon-tipped temporary pacemaker is recommended for rotablation to the RCA, a dominant LCx, left main stenoses, a vessel providing collaterals to AV nodal branch flow, in a critically sick patient, and in rota to sole-surviving vessels.^77^ Meticulous pre-procedure preparation with the “D-R-A-W” technique (Drip-Rotation-Advancement-Wire) must be performed. It is recommended that Rotawire™ floppy be used for all lesions except in ISR or ostial lesions. When crossing with a microcatheter is unsuccessful, one of three techniques may be useful. 1. The new Rotawire™ Drive wire helps in direct wiring. 2. Hubbing the microcatheter as close to the lesion as possible wiring with a Rotawire™ directly. 3. Using a small profile balloon to dilate the lesion at low pressure to create space for the microcatheter to cross the lesion. In situations where these methods fail, use of laser atherectomy with a standard workhorse wire and then attempting RA is recommended. Rotational atherectomy should be performed away from the radiopaque portion of the rota wire. No other wire must be present in the path of atherectomy. We strongly recommend short 20-s duration passes of rotational atherectomy with at least 1–2 min of intervening period between runs to facilitate better distal flow. A “pecking” motion is optimal for good atherectomy, while preventing burr entrapment or inadvertent advancement. Particular attention to the speeds during atherectomy are important, with optimal speeds being 1,40,000–1,60,000. Higher speeds lead to higher incidence of complications like perforation, activation of platelets leading to slow-flow. Deceleration beyond 5000rpm *are strongly discouraged and those beyond 10,*000rpm are to be avoided (indicated by a yellow hollow triangle and solid triangle warning on the console display). It is also strongly recommended that rotational atherectomy be completed with a “polishing run”. Use of Dynaglide or rotational atherectomy within the guide is to be avoided unless in case of ostial lesions where atherectomy may need to begin from within the guide. For early career operators, use of RotaPro may shorten the learning curve, with commands performed exclusively manually.
OA is another modality of athero-ablation, where a diamond coated crown rotates in an elliptical fashion over an 0.014” wire (ViperWire**™**), controlled by a hand-operated console. The device operates on a unique principal of differential sanding. Due to the presence of diamond coating in both the front and the back of the crown, OA has the ability of bi-directional ablation (i.e. forwards and backwards). The diameter of ablation depends on the speed of rotation, with higher speeds providing a larger diameter of ablation. This eliminates the need for up-sizing and exchange of equipment. Additionally, the oblong or elliptical orbit could be advantageous in severely calcified, eccentric lesions. Other potential advantages include the release of particles of smaller size (<2 μm), and lower no-reflow rates due to continuous blood flow being maintained during OA. However, lesion crossability of OA is less favourable compared to RA.
OA has proven to be a safe and efficacious modality in calcified lesions. ORBIT I was a non-randomised study in 50 patients undergoing OA for PCI in calcified lesions.^78^ OA demonstrated a 97 % procedural success rate (<20 % residual stenosis rate), with major complications (one major dissection and two perforations) seen in 3 patients. The 6-month MACE rate was 12.1 %.^78^ The ORBIT II study further established the safety and efficacy of OA in de novo calcified lesions.^79^ Amongst 443 patients, stent delivery occurred successfully in 97.7 % of cases with <50 % stenosis in 98.6 % of subjects. A total of 89.6 % patients experienced freedom from 30-day MACE, which was higher than the pre specified primary safety goal of 83 %. The primary efficacy endpoint of <50 % residual stenosis without the occurrence of in-hospital MACE was seen in 88.9 % patients.^79^ The 2-year MACE rate was 19.6 %.^80^ A recent single-arm prospective trial examining the use of a novel microcrown-based OA on 100 patients showed efficacy and safety equivalent to that seen in ORBIT II (procedural success of 85 % vs 88.9 %, p = 0.30 and in-hospital MACE rate of 14.0 % vs 9.8 %, p = 0.21, respectively) potentially improving device deliverability in the future.^81^ The recent ECLIPSE trial compared the use of OA versus balloon angioplasty in lesions where either was deemed possible. The trial did not show a difference in the primary imaging outcome of lesion expansion at 1 year (7.67 mm^2^ vs 7.42 mm^2^, p = 0.08) or in the primary clinical outcome of target lesion failure at 1 year (11.5 % vs 10.0 %, p = 0.28). Higher all-cause and cardiovascular mortality at 30 days were seen in the OA arm, with two deaths related to the device and two deaths possibly related to the device. Notably, the trial only included patients where equipoise between conventional PCI and OA existed, and densely calcified lesions where OA was clearly required up-front, were excluded. Therefore, a routine strategy with up-front OA in all calcified disease, therefore, is not recommended.
OCT-based studies have depicted atherectomy by OA to result in endovascular lacunae, akin to the effects of RA, with deeper lacunae being seen in OA.^82^ Furthermore, post-atherectomy modification in the form of gutters (defined as depressions 0.5–1 mm in depth and <3 mm in length) were seen with OA. OA therefore represents a safe and efficacious alternative to RA in carefully selected cases, with the aforementioned procedural advantages. Propensity-matched clinical endpoint comparisons have also been studied. A recent observational study comparing the safety profile of OA versus that of RA revealed less MI in patients undergoing OA (6.7 % vs 13.8 %, p ≤ 0.01) in propensity-matched cohorts.^83^ Furthermore, patients undergoing OA received less fluoroscopy times p ≤ 0.01 and less death on discharge (p = 0.01), respectively.^83^ Alternatively, another recent study showed OA to have similar 1-year MACE outcomes [16.30 % vs 21.66 %; aHR 0.79 (0.54–1.17), p = 0.25), compared to RA with a slightly higher risk of dissections and perforations.^84^ The recent OCT-based DIRO trial randomised patients with calcified lesions (with >180° calcium arc) to RA versus OA. The RA group had significantly higher stent expansion (99.5 % vs 90.6 %; p = 0.02.^85^ However, the sample size was small (n = 100), and up to 32 % lesions did not have a pre-atherectomy OCT assessment due to uncrossability.^85^ Overall therefore, the choice between OA and RA still remains based on lesion morphology and operator experience, with OA use being restricted largely to severely eccentric lesions.
Optimal technique: *We recommend the same optimal technique tips for OA as in RA. However certain distinctions deserve mention. Guide selection is based on other adjunct equipment as the device is itself 6 French compatible. Owing to the nature of atherectomy, slower passes-roughly of 1-*2 mm/s are suggested. Secondly, atherectomy-of 3mm forward and then 1mm backwards-is recommended. The rotation speed is determined by the size of the vessel, but is much slower than rotational atherectomy (80,000–1,20,000rpm). The cumulative atherectomy time of each OA crown must be under 5 min, following which, the crown must be replaced with a new one. Finally, the entire assembly is manual with no foot pedal, although this difference is mitigated now with the RotaPro^TM^ device.
Moderately calcified vessels can also be treated with Excimer laser therapy which comprises of high-energy, short wavelength (308 nm) ultraviolet light. Using Xenon Chloride gas, laser therapy acts via a photocoagulation effect-resulting in breakage of carbon bonds, a photothermal effect-generating vapour from intracellular water, and a photomechanical effect-generating destructive bubbles at the catheter tip.^86^ The laser exerts its effects over a short penetration length (<30 μm) for safety and control. The system is compatible with standard 0.014” workhorse coronary guidewires, and is available in 4 sizes- 0.9 mm, 1.4 mm, 1.7 mm and 2.0 mm with the latter two sizes requiring 7F guides. Concentric catheters are generally preferred whereas eccentric catheters may be selected for eccentric or focal lesions. The use of LA requires operators and patients to wear protective eye equipment. Furthermore, LA requires a continuous saline flush to achieve a field completely devoid of blood or non-ionic contrast. Operators typically may use up to 20 % contrast- 80 % saline mixtures in most lesions. This is due to the risk of dissection when large macromolecules (such as contrast or blood proteins) absorb the laser energy. However, higher concentrations of contrast may be required in recalcitrant lesions. Ablation with laser generates small particles of size <10 μm, resulting in low risk for no-reflow.^86^ The use of higher contrast-saline ratios may result in larger bubbles being generated. Laser activation lasts 5–10 s followed by an automatic cooling period of 5–10 s. Following this, an audible alarm signal is given off, after which, the next laser burst can be performed.
LA has been typically used in severely thrombotic lesions where the risk of no-reflow is high, and in balloon- or wire-uncrossable lesions. It must be noted however, that the laser energy does not itself debulk calcified plaques but modifies non-calcified fibrous or atheromatous material around the calcified areas, thus facilitating lesion dilatation.^86^ Apropos, imaging based studies have shown that unlike in other atherectomy techniques, production of calcium fractures may not be seen. Thus, also, the technique may prove to be suboptimal in extensively calcified lesions with minimal non-calcified plaque.
Data regarding the use of LA has been sparse. Two early observational studies on LA assisted angioplasty versus POBA alone, which also included calcified lesions, revealed a procedural success rate of 77.2 % and 88 %, respectively. The risk of coronary dissection was 6.9 % and 4.3 %, respectively.^87^^,^^88^ In the more contemporary LEONARDO study, however, LA was shown to have a high procedural success rate (93.7 %) in balloon-resistant calcific lesions and PCI with DES, with no incidence of coronary dissections.^89^ However, the limitations of ELCA in severely calcific lesions were reiterated in the recent ROLLER COASTER EPIC 22 randomised trial.^90^ A total of 171 patients with calcific lesions, with predominantly severe calcium (82 %), were enrolled. Procedural success rate and final minimum stent area (RA, 5.5 ± 2.1 mm2; IVL, 5.4 ± 1.8 mm2; ELCA, 5.1 ± 1.8 mm2) were similar among the 3 arms. In terms of stent expansion, ELCA failed to achieve non-inferiority in comparison with IVL and RA.^90^ However, ELCA may be particularly useful in high thrombotic calcified lesions. Additionally, recent studies have shown particular use of LA in ISR and underexpansion.91, 92, 93 It is likely that LA favourably alters the lesion compliance, which could be especially useful in long-standing ISR lesions.
Optimal Technique: *The 0.*9mm *and 1.*4mm *catheters are 6F compatible, whereas 1.*7mm *and 2.*0mm require 7F guiding catheters. We recommend an artery-to-laser-catheter ratio of 2 to 3 in particularly large vessels, but most lesions are usually amenable to atherectomy with a 0.9 mm catheter. Wiring with non-polymer jacketed wires is required owing to risk of damage to the coating during LA use. We recommend starting with low fluence and pulse rate settings and escalating as per need (fluence to be escalated first). We recommend up-front usage of the 80mJ/mm fluence in cases of under expanded stents, dense calcification or calcific CTO with wire uncrossability. The device can perform debulking in antegrade and retrograde fashion. Advancement must be slow at 1 mm/s. The laser atherectomy of the lesion must be synchronous with a 10ml saline flush to clear out blood and contrast. However, if higher energies or focussed energies are required, careful LA with a balloon blocking technique may be employed, as laser is safe with a second wire in-situ. The nose cone of the laser must be pointing coaxially at all times to avoid ablation of the vessel wall.
A Calcific Nodule
Calcific nodules represent a particularly challenging subset of coronary anatomy. They are convex protrusions into the lumen with irregular surfaces and a calcified leading edge. They are classified into 2 categories-eruptive nodules, characterised by intimal disruption and possible luminal thrombus, and noneruptive nodules, with an intact intima.^94^ The presence of intimal disruption portends a risk of acute coronary syndrome in these patients and thus carries much greater clinical significance. The use of IVI can be useful to determine the presence and the adequate debulking of the nodule. This is particularly important to reduce risk of future re-protrusion and ISR. The optimal techniques to debulk calcific nodules are still unclear, however, atherectomy techniques appear most attractive. While using atherectomy techniques, it is beneficial to consider slower or greater number of passes to attain more comprehensive debulking. Also, manipulation to a more favourable wire bias, or using extra support wires are recommended. Alternatively, IVL has also been shown to be useful and safe in calcific nodules, with greater pulses being used if required.^63^ Similarly, in a subgroup analysis from the DISRUPT CAD III trial, IVL showed no difference between MLA with or without calcified nodule, indicating that IVL may be useful for CN lesions.^64^ In another recent observational study across 54 nodular lesions, OA, RA and IVL demonstrated similar minimum stent area at the nodule site (7.17 ± 0.43 mm^2^, 6.46 ± 0.49 mm^2^, 7.86 ± 0.56 mm^2^, respectively; p = 0.55).^95^ A recent algorithm has been proposed by Yasumura et al, recommending RA or OA ± IVL for minimal lumen diameter of <1.5 mm at the nodular site with a large calcium arc (>270°), whereas for larger lumen diameters and a large arc, up-front large burr RA or high speed OA may be tried, with IVL to be added if required. In those with nodules of a smaller calcium arc, when the lumen diameter is < 1.5 mm, OA/RA may be attempted, whereas in those with a larger diameter, up-front IVL may be tried.^95^BIn-stent Restenosis
Several mechanisms can potentially predispose to ISR including neointimal hyperplasia, neoatherosclerosis and stent under expansion as distinguished on IVI. For neointimal hyperplasia, BA techniques (CB, SB, HPB) may be used. In case of neoatherosclerosis, modification with BA techniques and DES implantation may be required. Though RA or OA is not conventionally approved for ISR, they may be used off-label for the same. Another option is laser atherectomy with eccentric catheter use or deliberate contrast injection for controlled cavitation.^96^ Laser may be particularly useful in long standing ISR to improve lesion compliance and thus facilitate further plaque modification with BA techniques.CBifurcation lesions
Calcification can significantly impact device delivery and optimal PCI results in bifurcation lesions. Calcification in bifurcations can be challenging owing to difficult angulation, issues with wire recrossing, possible plaque shift and vessel closure. Following imaging of the main branch (and of the side branch if required), PCI techniques may be planned. POBA or atherectomy techniques may be used as per the pattern and site of calcification. The procedural techniques employed are similar to the usage in single vessel lesions. Additionally, “halfway rotational atherectomy” may be performed in particularly angulated bifurcations.^97^DAorto-ostial lesions
Ostial lesions are often calcified and difficult to treat. The use of coaxial and “non-aggressive” guiding catheters helps avoid issues related to damping. Adequate lesion preparation is of paramount importance due to the area subtended by these lesions, and due to ostial lesions being prone for ISR. BA techniques (CB, SB, IVL, HPB) offer good results due to good anchoring and expansion in these lesions. When atherectomy methods are considered, short RA runs may be preferred to facilitate delivery, followed by other BA techniques to further optimise the bed.EThrombotic lesions
In up to 26 % of acute coronary syndromes, thrombotic lesions may also contain moderate to severe calcification.^98^ IVI for these lesions is strongly recommended to better distinguish between residual thrombus and calcification. For management of the thrombotic component, adequate thrombus clearance up-front may be of particular benefit if the delivery of thrombosuction equipment is feasible. Embolic protection may also be considered. In the setting of dense thrombus burden or inability to deliver equipment, ECLA is the preferred modality to eliminate thrombus as well as modify plaque. Alternatively, if delivery is possible, calcium modification may be achieved by modified balloon angioplasty techniques (CB, SB, IVL, HPB).
Calcified coronary lesions represent a unique entity characterised by increased complexity during intervention and higher risk of adverse events. Several adjunct modalities currently exist to facilitate and optimise PCI in calcified lesions. These techniques range from balloon angioplasty techniques to debulking techniques, each with its advantages and disadvantages. Additionally, the use of intravascular imaging is useful in defining the pattern of calcification and determining the appropriate adjunct technique to be used to complete PCI successfully.
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