Calcification detection and assessment

Angiography is a limited sensitivity tool to detect coronary artery calcium. Unlike angiography both the IVUS and the OCT have higher sensitivity and specificity to assess the characteristics and degree of calcification, which are basic aspects to determine the therapeutic options.²,⁹ Table 1 shows the differences of these 2 intracoronary imaging modalities regarding calcium detection. The main difference between the 2 is that, since calcium creates posterior acoustic shadowing on the IVUS, calcium thickness cannot be properly assessed. As alternative marker, the presence of reverberations on the IVUS has been associated with the presence of thinner calcium layers (< 0.5 mm). On the OCT, parietal calcium does not create posterior acoustic shadowing and, therefore, its thickness can be assessed accurately. Nodular calcium, however, creates a shadow in both the IVUS and the OCT (figure 1).

Figure 1. Coronary artery calcium assessment with IVUS and OCT. A: Parietal calcium on the OCT, low reflectivity structure with demarcated borders (asterisk). B: Parietal calcium on the IVUS, hyperechogenic structure with posterior shadowing. C: Calcium nodule on the OCT, structure protruding into the lumen with posterior shadowing. D: Calcium nodule on the IVUS, structure protruding into the lumen with posterior shadowing. 

Different scoring systems have been developed for both intracoronary imaging modalities (table 2) including the characteristics of calcification that have been associated with stent underexpansion. The first OCT suitable scale ever developed includes 3 different parameters: calcium arc > 180º (score = 2), length > 5 mm (score = 1), and thickness > 0.5 mm (score = 1). Lesions with scores > 2 have a higher risk of stent underexpansion if proper plaque preparation is lacking.⁵ A similar scale has been developed for IVUS using 4 different criteria: calcium arc > 270º with > 5 mm in length (score = 1), calcium arc > 360º (score = 1), presence of calcified nodule (score = 1) and adjacent vessel < 3.5 mm (score = 1). Scores ≥ 2 are indicative of the need for plaque modification prior to stenting.¹⁰

Selection of plaque modification techniques under intracoronary imaging modality guidance

The characteristics of calcium as seen on the intracoronary imaging modalities can contribute to the selection of the most adequate plaque modification technique. There is in depth information on this aspect in the last section of the document but, overall, lesions where calcium does not have underexpansion risk criteria can be treated with high-pressure or modified balloons (scoring, cutting). However, if these criteria exist it will be necessary to use more advanced plaque modification techniques. Added to these criteria, we should also mention calcium depth since some imaging modalities only act on the superficial not deep layer of the plaque.

Optimization of stenting under intracoronary imaging modality guidance

Both the IVUS and the OCT allow us to determine whether proper stent expansion has been achieved. This is especially relevant in calcified coronary artery lesions that happen to be the ones that are most associated with stent underexpansion, the parameter most strongly associated with stent failure.¹¹ Proper apposition and lack of dissection or significant border hematoma, as well as proper lesion coverage are other optimization parameters under intracoronary imaging modality guidance that should also be assessed after stenting.¹²

Rotational atherectomy

The rotational atherectomy (RA) technique uses a metal olive-shaped burr covered with diamond crystals in its distal third that rotates at high speed and performs a differential cut when advancing through the vessel (figure 2A) while pulverizing calcified tissue and preserving the adjacent elastic tissue.¹³

Figure 2. Plaque modification devices. A: Rotational atherectomy device. B: Orbital atherectomy device. C: Coronary laser device with the 2 existing console models. D: Intracoronary lithotripsy device. Modified with permission from Cubero-Gallego et al.¹³  

It appeared over 30 years ago to facilitate the management of coronary artery lesions by reducing plaque burden. Early enthusiasm turned into an elevated use of RA in different settings without the proper scientific back-up. This triggered suboptimal results¹⁴ that reduced its use to highly selected cases only. Through all these years, RA has evolved with technological improvements, and also of the technique itself, as well as the selection of patients.

Currently, the ROTAPRO system (Boston Scientific, United States) is available. It has made the technique easier because it has replaed the pedal of the early version for a button placed on top of the olive-shaped burr advancer. There is another button on the side of the advancer to change to the Dynaglide mode (rotation at low revolutions is advised to introduce and remove the burr). Console is smaller and comes with a digital screen. Size of the burrs is between 1.25 mm and 2.5 mm, and they are compatible with 6-Fr-to-8-Fr catheters based on the size of the olive-shaped burr that advances on a 0.009 in specific guidewire (0.014 in the radiopaque side) of which 2 different versions exist (RotaWire Floppy and RotaWire Extra-Support) that should be used depending on the characteristics of the plaque and support needed.¹³

The main indication is to treat extremely calcified non-crossable or non-dilatable coronary artery lesions with balloon. Probably, the optimal scenario is a concentric calcified lesion with a smaller luminal area compared to the olive-shaped burr. Eccentric angulated lesions are less favorable since they are associated with a higher risk of complications.¹³,¹⁵ It can be used as a primary or a bailout strategy after “balloon failure”. The primary strategy has been associated with shorter procedures, less radiation and contrast, and probably lower cost regarding the material used.¹⁵

The target of RA has also changed from the old idea of removing as much plaque as possible (debulking) to the modern approach of modifying plaque to “facilitate” the PCI. Technical recommendations to perform RA have evolved too. Current recommendations are shown on table 3.¹⁶

The most common complication is slow/no-flow although its rate has dropped down to 2.6%.¹⁷ It is due to debris embolization towards microcirculation and there is higher risk in long lesions where multiple and prolonged passes with large olive-shaped burrs are performed without proper pauses among them and in the presence of a poor distal vessel. The management of dominant right coronary or left circumflex coronary arteries can be associated with transient conduction disorders. Severe complications like burr entrapment, perforation, and coronary dissection are rare.¹³ Factors predisposing burr entrapment are lesion severity, steep angulations, and the use of very small burrs. Tortuosity and the lack of guide catheter coaxiality in the management of ostial lesions can trigger dissections and coronary perforations.

Although RA has demonstrated that it facilitates PCI with higher rates of success compared to balloon angioplasty, No clinical benefit has been yet confirmed.¹⁸-²¹

To analyze its results we should mention that RA has been used in patients of higher clinical risk with more complex coronary artery lesions.²² Another aspect we should take into consideration is the high percentage of cases where this technique was used as a bailout strategy (12% to 50%)²⁰,²¹,²³ meaning that without RA these cases would not have been performed or had had worse results. Although ongoing trials are studying the advantages of elective or bailout RA, proper patient and lesion assessment should lean towards increasing its elective or earlier use with a potential beneficial impact on clinical outcomes.²⁴

In conclusion, when performed under the current recommendations RA is a safe and effective procedure. It should become part of our therapeutic arsenal in our cath labs with trained personnel for proper use.

Orbital atherectomy

The Diamonback-360 (OAS) device (Cardiovascular Systems, United States) is a diamond-coated bidirectional orbital crown that uses a combination of centrifugal force (by creating elliptical orbits) and friction to the surface to modify the calcified plaque and increase compliance (figure 2B). Also, with the pulsatile impact of the crown after speeding up, microfractures can occur that eventually modify deep calcium layers (figure 2B and figure 3). That is why a single 1.25 mm crown can treat vessels from 2.5 mm up to 4 mm.

Figure 3. Characteristics of orbital atherectomy catheter and its effects. (Modified with permission from Cardiovascular Systems.²⁵) 

Compared to the remaining plaque modification techniques, this orbital atherectomy (OA) has arrived late to our country and our experience is still scarce.

Its main indication is to treat no-dilatable calcified coronary artery lesions.²⁶

Preparation is very similar to RA, but here a specific guidewire is needed, the Viper-Wire. Crown advances with the Glide-Assist system (rotation at low revolutions) until coming close to the lesion. Another distinctive feature of this device is its antegrade and retrograde ablation functionalities. Unlike RA, the speed at which the device moves forward needs to be very slow (between 1 mm and 3 mm per second) to guarantee good procedural results and reduce complications.¹⁷,²⁶ The mechanism of action of OA consists of the crown elliptical rotation that achieves a gradual increase of orbital diameter as rotation speed increases from 80 000 rpm up to 120 000 rpm. Cycles ≤ 30 seconds are advised (it comes with a sound warning signal to end the cycle) with pauses between 20 and 30 seconds among them that can duplicate in cases of poor hemodynamic tolerance.²⁶ The continuous infusion of a lubricant solution is necessary to minimize thermal lesions during OA. Also, 18 mL/min are administered to cool the device down and get rid of debris, thus reducing the chances of ischemia and distal embolization.¹³,²⁶,²⁷

Complications are similar to those of RA. However, the possibility of retrograde application reduces the chances of crown entrapment and the risk of dissection or perforation in angulated or ostial lesions. The rate of perforation is between 0.7% and 2%.²⁸,²⁹ Theoretically speaking, the debris created by OA is smaller compared to the debris created by RA. This added to the fact that the crown does not stop coronary flow during atherectomy reduces the risk of slow/no-reflow and endothelial thermal lesion.²⁷ However, transient conduction disorders are not rare when dominant right coronary or left circumflex arteries are treated.

Current evidence available is based on the ORBIT I³⁰ and ORBIT II²⁸ clinical trials where OA obtained good results regarding procedural success (94% and 89%, respectively) with higher rates of major adverse cardiovascular events (MACE), and target lesion failure of 23.5% and 7.8%, respectively, at 3 years.³¹ Afterwards, the COAST trial²⁹ was conducted where the new MicroCrown system was used. A total of 100 patients were included with rates of procedural success and MACE of 85% and 22.2%, respectively, at 1-year follow-up. We are waiting to see the results from the ECLIPSE trial that will randomize a total of 2000 patients with severe calcifications to receive OA or balloon predilatation prior to by drug-eluting stent implantation.

In conclusion, OA is another calcium plaque modification technique with potential technical advantages like having only 1 size of crown compatible with 6-Fr to treat all lesions and with pull-back capabilities. Although there are insufficient data from comparative studies, choosing this technique will depend on the profile of the patient and the lesion to be treated, the intracoronary being an essential aspect.

Excimer laser

Excimer laser coronary angioplasty (ELCA) is based on a xenon chloride laser that generates short ultraviolet pulses of 308 mm that only penetrate 50 µm in depth, which makes it safer compared to old continuous-wave-near-infrared lasers. It modifies the plaque through a triple mechanism: photochemical (by breaking molecular binds), photothermal (through tissue vaporization), and photokinetic (through the expansion and collapse of the bubble of the catheter tip as it moves forward). Fragments released are < 10 μm, which minimizes microvascular damage after being absorbed by the reticuloendothelial system.

The system currently used is the CVX-300 Laser System (Philips) although there is already a new generation one, the LAS-100 Laser System (Philips) that will be replacing it shortly (figure 2C). There are different sizes of catheters available (0.9 mm, 1.4 mm, 1.7 mm, and 2.0 mm) (table 4). The selection of the catheter depends on the type of lesion and size of the vessel (catheter to vessel diameter ratio, 0.5-0.6) being the 0.9 mm catheter the most widely used for its lower profile and because it can reach higher fluency (80 mJ/mm²), pulse repetition rate (80 Hz), and longer application durations (10 seconds with 5-second rests), which increases the chances of success in fibrous calcific plaques.³²,³³

Before being used, it is necessary to calibrate the console and then the catheter. In both cases, health professionals and patients should use protective glasses to prevent eye damage. Afterwards, a 0.014 in intracoronary guidewire is inserted until it reaches the lesion. There is a monorail system to facilitate moving forward. Energy is released through the catheter distal border as it slowly advances (0.5 mm/second) to modify the plaque. Catheter withdrawing can also be applied. It is important to optimize support to ensure that the catheter advances. There is no limit in the number of pulses that can be administered since the more it is used, the stronger the effect. However, there is also a higher risk of complications involved. Some authors suggest a maximum of 12 applications.³³ The state of the vessel should be assessed after each application. Regarding the selection of parameters, traditionally it started at 45 mJ/mm², and 25 Hz. However, more and more operators prefer higher energies and initial frequencies especially to treat resistant or calcified lesions.³³

Before and during the applications, the blood vessel should be washed, and contrast administered through the infusion of a physiological saline solution (1 mL/s to 3 mL/s). In resistant lesions with severe calcification or underexpanded stents, more energy may be needed. This can be reached by not washing the blood with the physiological saline solution or even administering contrast during applications (the so-called “explosion technique”). This technique reaches maximum power although it increases the chances of complications. Some authors³³ recommend it as the first option to treat non-thrombotic lesions, although it seems reasonable to spare it for ELCA-resistant lesions with saline infusion.

Traditionally, the indications for ELCA have been categorized into 2 different groups: “thrombotic” (not discussed in this document) and “calcified” lesions (non-thrombotic like in-stent restenosis, chronic total coronary occlusions, calcified lesions, etc.). The latter can be categorized into non-crossable or non-dilatable lesions:

Cutting and scoring balloons

Cutting balloons (CB) are plaque modification devices that appeared as an alternative to old coronary angioplasty balloons.⁴⁰ Their objective is to achieve controlled ruptures of the plqeu (through incisions in fibrocalcific tissue) (figure 4), thus facilitating balloon expansion, minimizing damage to the intima layer, and reducing stenosis.¹⁸,⁴¹

Figure 4. Rotacutting technique. Rotational atherectomy (RA) effect and cutting balloon (Rotacutting) with greater plaque modification and minimum lumen area. 

There are 2 different types: CB and scoring balloon (BS). Their use has been described in different settings like in-stent restenosis, aorto-ostial lesions, bifurcations, and small vessels associated with the use of drug-eluting stents.⁴²

The main limitations of CBs are their worst navigability and crossing profile compared to conventional balloons. However, over the past few years, both aspects have improved. SBs are associated with better navigability compared to old CBs.

The most dreaded complication is the rupture of coronary artery, although it has significantly increase following its use.

The main difference among the different devices lays in their different external atherotomy elements as described herein (figure 5).

Figure 5. Characteristics of modified balloons. A: Cutting balloon (Boston Scientific, United States). B: WOLVERINE (Boston Scientific, United States). C: AngioSculpt (Spectranetics, United States). D: Scoreflex (OrbusNeich, Hong Kong). E: Grip (Acrostak, Switzerland). F: NSE-Alpha (B.Braun, Germany). G: Naviscore (iVascular, Spain). 

Very high-pressure balloons

The NC very high-pressure balloon (VHPB) OPN (SIS medical, Switzerland) is a double-layer balloon for homogeneous expansion at extremely high pressures without increasing its diameter (from 2 mm to 4 mm) with a rated burst pressure of 35 atm, although the manufacturer's testing rated burst pressure limit is 45 atm (table 5).⁴⁶

The VHPB has been used for over 10 years now and it has proven safe and effective in up to 40 atm in extremely calcified coronary artery lesions where other devices have failed or in stent underexpansion. Success rates are as high as 75% to 100% without evidence of dissection, perforation or balloon bursts in small case series.⁴⁷ Compared to conventional NC balloon, it can achieve minimum luminal diameters and major acute gains with less residual stenosis in non-dilatable lesions.⁴⁸

The largest registry ever conducted to this date included 326 patients with non-dilatable lesions treated with VHPB after failed NC balloon. Patients were categorized into 2 groups: those who responded to pressures between 30 atm and 40 atm, and those who responded with pressures > 40 atm. Procedural success was reached in up to 96.6% of the patients. A total of 53% of the patients responded to pressures between 30 atm and 40 atm while the remaining 47% did so to pressures > 40 atm. A total of 180 patients were treated with intracoronary imaging modalities and 106 of these showed calcifications > 270º. In this subgroup of patients, the pressured needed for optimal expansion was > 40 atm in 78.3% of the cases. Three patients (0.9%) showed coronary artery ruptures that resolved with prolonged inflation or covered stent implantation. In the 3 cases, the ruptures occurred during predilatation and were associated with balloon bursts with pressures between 30 atm and 40 atm. This is suggestive that perforations don't seem to be associated with inflation pressure but with the characteristics of the plaque or the vessel size estimate that was angiographic in the 3 cases reported.⁴⁹

The ISAR-CAL trial⁵⁰ was published back in 2021. It randomized 70 patients with extremely calcified coronary artery lesions and failed predilatation with NC balloon to receive a SB or a VHPB. The study primary endpoint was to compare stent expansion on the OCT. No differences were reported in the percentage of stent expansion. However, differences were seen in angiographic secondary endpoints like improved minimum luminal diameters and residual stenoses favorable to VHPB.⁵⁰

Finally, chronic total coronary occlusions are the pinnacle of calcified complex lesions. In the PLACCTON trial the use of the VHPB both alone and with other plaque modification techniques was safe and effective in selected cases with chronic total coronary occlusions.⁵¹

In conclusion, the VHPB is a safe and effective alternative to treat non-dilatable calcified coronary artery lesions. Randomized clinical trials better defining this device strategy of use and the remaining plaque modification techniques are lacking.

Intracoronary lithotripsy

Intracoronary lithotripsy (ICL) system consists of a specific balloon catheter (Shockwave Medical, United States) connected to a rechargeable portable generator (figure 2D). The generator produces energy pulses that are transmitted to emitters placed inside the balloon. Pulses are emitted at a frequency of 1 per second up to a maximum of 10 pulses per application. Each balloon catheter can administer a maximum of 80 pulses. The catheter consists of a rapid-exchange semicompliant balloon with a 0.042 in crossing profile compatible with any 0.014 guidewires and 6-Fr guide catheters.

Its main indication is to treat calcified non-dilatable coronary artery lesions.

A 1:1: ratio between the vessel and balloon diameters is advised. Once it has been placed inside the lesion, the balloon inflates at 4 atm to secure proper contact between the balloon surface and the vascular wall to allow energy transfer. The balloon includes 2 emitters that receive an electric discharge from the generator that vaporizes the fluid inside generating sound waves that have a local effect. Each pulse releases the equivalent of 50 atm.

These waves run across soft tissues causing selective calcium microfractures at intima and media layer level. After pulse emission and the corresponding modification of calcium, the balloon inflates up to 6 atm to maximize luminal gain. Balloon catheter is only available at a length of 12 mm and comes in diameters of 2.5 mm, 30 mm, 3.5 mm, and 4.0 mm.⁵²

The greatest evidence available comes from the Disrupt-CAD III trial, a prospective registry that assessed the efficacy and safety profile of ICL in 431 patients with calcified lesions. The 30-day rate of MACE (death, infarction or target lesion revascularization) was 7.8% while the rate of effectiveness (procedural success with in-stent stenosis < 50%) was 92.4%. No patients with acute myocardial infarction or complex lesions were included in this study.⁵³ Recently, 12-month follow-up results have been published confirming rates of MACE and stent thrombosis of 13.8% and 1.1%, respectively.⁵⁴

Controlled break down of coronary calcium is the basis of treatment of ICL balloons. In a OCT substudy of the Disrupt-CAD II trial after ICL calcium fractures were seen in 79% of the lesions⁵⁵ compared to 67% of the lesions of the Disrupt-CAD III trial.⁵³

Although the use of ICL balloons has become very popular worldwide, information on its safety and efficacy profile regarding its use in complex settings is still scarce (acute coronary syndrome, chronic total coronary occlusions, bifurcations or aorto-ostial lesions). As a matter of fact, its use is often limited to isolated cases or short series.⁵² The main limitations of this system are its reduced crossing profile in extremely calcified or tortuous stenoses and difficult use in diffuse or multivessel lesions (due to the limited number of pulses per catheter and the different caliber of target vessels).

A recent trial assessed the use of underexpanded stents due to severe coronary artery calcification and confirmed angiographic success rates of up to 73%, which is lower compared to the 75% seen in native lesions⁵⁶ probably because it is more difficult to expand a calcified lesion when the stent has already been deployed. Therefore, regardless of the technique used, stenting is ill-advised until the lesion has been properly prepared. Also, the application of lithotripsy in this context, especially on freshly implanted stents, can cause structural damage to the polymer.⁵⁷ Another multicenter registry proved the device was successful 92.3% of the times in this type of lesions.⁵⁸ Mid- and short-term data on the safety profile of this technique are still lacking.

The combined use of ICL balloon and other plaque modification devices like RA,⁵⁹ OA⁶⁰ or ELCA⁶¹ has been described, and it seems like a very attractive strategy in cases where the ICL balloon cannot reach the target lesion.

In conclusion, ICL has grown exponentially in the management of non-dilatable calcified coronary artery lesions thanks to its safety and efficacy profile, and short learning curve. However, information on its use in complex scenarios and comparative results with other plaque modification techniques are still lacking.