New Technologies in Calcium Management in Coronary Artery Disease

INTRODUCTION

Coronary artery disease is a significant cause of morbidity and mortality globally, and calcified lesions present a formidable challenge in achieving successful revascularization.^[1,2] Percutaneous coronary angioplasty (PTCA) has come a long way since first performed in 1977 by Andeas R. Gruntzig and is being increasingly used in complex lesions and in high-risk substrates.^[3] Despite technological advances, calcified lesion remains difficult subset and is being encountered more frequently, as aging and sicker population such as chronic kidney disease patients, long-standing diabetes mellitus, and elderly are being taken up for angioplasty.

Presence of calcium limits vessel compliance and limits the technical success of the procedure due to suboptimal lesion preparation, difficult stent delivery, deployment, and stent expansion which leads to increased risk of instent restenosis and stent thrombosis along with higher procedural complications.^[4]

Diagnosis of presence and extent of calcification is first and foremost to plan the treatment modalities for optimal procedural success. Coronary angiography has a limited sensitivity (40– 79%) but a high specificity (55–95%) for identifying calcium.^[5] Calcification appears as dark linear shadows along coronary artery contours during fluoroscopy. Fluoroscopic calcium grading during angiography is categorized as none/mild when no calcifications are observed on coronary angiography (CAG), moderate when calcifications are visible only during cardiac motion before contrast injection, and severe when radiopaque areas are seen without motion, typically displaying a tram-track pattern.^[6]

INTRACORONAY IMAGING

Use of intracoronary imaging, in the form of intravascular ultrasound (IVUS) or optical coherence tomography (OCT) for calcified coronary lesion angioplasty has proved to be very important and helpful. Imaging provides important insights into lesion morphology, helps in lesion assessment, defining location, extent and distribution of calcium for proper preprocedural planning, helps stent optimization, and helps in picking up any immediate complication and its correction.^[7]

The 2021 American College of Cardiology (ACC)/American Heart Association (AHA)/Society for Cardiovascular Angiography and Interventions (SCAI) coronary artery revascularization guidelines give class II a recommendation for use of intracoronary imaging for procedural guidance for complex coronary stenting.^[8] ACC/AHA/SCAI updated comprehensive acute coronary syndrome (ACS) guidelines published in February 2025 have given Class 1 recommendation to use intracoronary imaging for complex lesions including calcified coronary disease.^[9]

IVUS

IVUS uses ultrasonic waves which give sequential cross section imaging of coronary arteries and help in assessment of lesion morphology and measurements. Calcium intensely reflects the IVUS beam, resulting in a hyperechoic (echo-dense) plaque that is brighter than the adventitia and obscures the deeper arterial layers with a shadow (post calcium shadowing).^[10]

Conventional IVUS system has a resolution of 100 microns and has tissue depth penetration of 4–8 mm. Newer IVUS systems now able to offer better resolution of up to 22 microns (Refinity, Phillips, OptiCross HD, Boston).^[11]

IVUS is also helpful following plaque modification to assess the fractured calcium after calcium modification or atherectomy as it produces reverberations signifying adequacy of the lesion preparation. Echo-dense plaques with shadowing are highly sensitive, whereas reverberations are highly specific for identifying modified calcium.^[12]

IVUS quantifies calcium by measuring the calcium arc in degrees and the length of the calcium deposit. It can also be semi-quantitatively graded based on presence of calcium in one, two, three, or all four quadrants. Quantitative gradation distinguishes between superficial and deep calcium, where superficial calcium is located within the inner 50% of the plaque and media, while deep calcium lies in the outer 50%. An IVUS scoring system aids in predicting stent under-expansion and pinpointing lesions that may require plaque modification before stenting to improve outcomes.^[13]

The morphological indicators on IVUS which guide about the need for calcium modification for optimal procedural success are −360° arc of calcium (calcium ring), calcium arc of >270° with calcium length longer than 5 mm, presence of calcium in smaller vessel (defines as diameter <3.5 mm), and presence of calcified nodule (CN) in the lesion.^[14]

High definition (HD) IVUS (OptiCross HD) is technically more advanced and is available now, provides better resolution imaging, is 5 Fr guide compatible, and has 6 mm penetration depth, providing greater details about the lesion morphology and presence of calcium.

IVUS + Near-infrared spectroscopy (NIRS) is dual mode IVUS catheter, equipped with NIRS, is further technological advancement, and is capable of defining plaque composition better (able to guide the lipid content in the plaque also) to guide highly informed decisions during percutaneous coronary intervention (PCI).^[15]

OCT

OCT is an imaging technique that uses infrared light waves, (unlike the sound waves utilized in IVUS) to reflect off the internal microstructure and provide detailed structural information of the artery and plaque.^[16] OCT offers image resolution that is 10 times greater than IVUS but has a shallower penetration depth of approximately 1.5–3.0 mm.^[17] On OCT, calcium appears as heterogenous low back scatter area with low attenuation and relatively clear cut borders. OCT aids in classifying calcium as deep, superficial, or nodular, and as either eccentric or concentric, facilitating the selection of the most suitable treatment approach for the specific lesion.^[18]

OCT-based calcium scoring utilizes a point system. ACC/AHA has given rule of 5 (now being evaluated further) based on arc, length and thickness of the calcium: A calcium arc >180° scores 2 points, a calcium arc between 90 and 120° scores 1 point, calcium length >5 mm scores 1 point, and the presence of a CN scores 1 point. CN is a mass of calcium protruding in the lumen, of coronary artery, which might appear as a radiolucent defect on angio mimicking thrombus and is shown to be associated with adverse major adverse cardiovascular events (MACE).

A total score of >4 on OCT or >2 on IVUS indicates the need for calcium modification to achieve optimal procedural success.^[4,19]

TREATMENT MODALITIES

Severe calcified lesions can hinder lesion preparation, stent delivery, and stent expansion, leading to suboptimal outcomes, increased periprocedural complications, and a higher risk of long-term adverse events such as stent thrombosis and restenosis. A meta-analysis of 16 randomized controlled trials revealed that PTCA in severely calcified coronary lesions is associated with higher mortality, increased rates of periprocedural myocardial infarction, reduced likelihood of complete revascularization, and serves as an independent predictor of poor prognosis.^[20]

Advances in technology have introduced new methods to address the challenges of treating coronary artery calcium (CAC) in the form of:

• Balloon based therapy (Non-compliant [NC], OPN, cutting balloon (CB)/Scoring Balloon, and intravascular lithotripsy [IVL])

• Atherectomy (with rotational atherectomy (ROTA) or orbital atherectomy [OA])

• And laser (Excimer laser coronary atherectomy [ELCA]).

These innovations focus on ablating or fracturing calcified plaques, enhancing procedural success, and improving stent expansion. This leads to a larger minimum stent area (MSA), a key indicator of better short- and long-term outcomes following PCI.^[21]

Using plain balloon catheters for treating severely calcified coronary lesions significantly increases the risk of procedural failure and associated complications due to inadequate lesion preparation and poor device deliverability. The varying degrees of calcification within the lesion cause uneven force distribution on the vessel wall, raising the likelihood of coronary dissection, possible vessel perforation, and higher rates of MACE.^[6] NC balloons are more effective for mild-to-moderate cases of CAC; it might create dissection in media and help in modifying the vessel compliance. One should use relatively smaller-sized balloon (balloon/artery ratio <1) while using NC balloons, with inflation pressure only gradually escalated. Stent deployment should not be done until lesion is uniformly expanded without any dog-boning seen in two orthogonal views for optimal outcome.^[22]

Ultrahigh pressure balloon, OPN NC balloons are relatively newer devices, useful in moderate to severe CAC. These are double layered balloons and can be inflated up to 35–40 atmospheres, with a high success rate in calcific, non-dilatable lesions, and also work for under-expanded stents. Best to undersize the OPN balloon by 0.5 mm for predilatation and using 1:1 size for post dilatation as required. However, they are not very useful in severe calcification and work best where the calcium arc is <180° and calcium thickness is <0.5 mm, underlining the importance of better imaging while treating calcified lesions.^[23]

CUTTING AND SCORING BALLOONS

Special balloons, such as cutting balloons (flextome and wolverine), are designed for treating calcified coronary lesions. These balloons are equipped with three to four sharp metal microtome blades mounted on a NC balloon. During inflation, the blades incise and score the plaque, creating discrete lesions. This process induces controlled dissection of the plaque, improving vessel compliance and promoting greater expansion of the lesion. Best to undersize the cutting balloon by 0.5 for predilatation.^[24] The cutting balloon to optimize predilatation for stenting (COPS) trial compared cutting balloon to NC balloon and showed that better MSA is achieved (though it was not statistically significant).^[25]

Scoring balloon (scoreflex and angiosculpt) is an alternative to the cutting balloon. These are semi complaint balloons covered by flexible nitinol wires wrapped around, that incise the plaque when the balloon is inflated. Angiosculpt has a low crossing profile and is a more flexible alternative as compared to cutting balloons. Scoring balloons are also useful in ostial lesions, as they reduce the risk of barotrauma leading to lesser risk of coronary perforation and dissection.^[26,27]

Cutting balloons, with sharp blades, are more effective in treating resistant calcified lesions, while scoring balloons provide controlled plaque scoring, improving stent expansion. Studies suggest cutting balloons have higher success in plaque modification, while scoring balloons may have a lower complication rate and are often preferred for less complex lesions.

IVL

IVL is one of the most modern calcium modification balloon based technique. Lithotripsy has been available for the treatment of ureterorenal calculi for long time and has been now adapted to be used in calcified arterial lesions (coronary and peripheral) with the Shockwave IVL catheter (shockwave medical).^[28] The original catheter is 6 Fr guiding compatible and is single use, monorail catheter which consists of a semi-complaint balloon with two emitters which are placed diagonally opposite at proximal and distal end of the balloon. The balloon length is standard 12 mm and is available in sizes ranging from 2.5 to 4 mm, to be used in vessel sizes of the same diameter. It is sized 1:1 to vessel diameter and balloon is inflated to sub-nominal pressure @ 4 atm just to provide apposition with vessel wall without going high pressure (avoiding risk of barotrauma). When the device is switched on, it generates acoustic pressure wave @ 1 pulse/s, in bundles of 10 impulses in one go, with minimum pause of 10 s in between.^[29] These acoustic waves travel circumferentially through the lesion and vessel wall, leading to fracture of both superficial and deep calcium plaque, (creating a pressure of approximately 50 atms), without much interaction with adventitia. This results in better vessel compliance after superficial and deep calcium fracture, less recoil leading to better stent expansion, MSA, and luminal gain.^[28] DISRUPT CAD Trials (1–4) have established the safety and efficacy of IVL therapy in contemporary practice.^[30]

SHOCKWAVE C2⁺ is the latest addition to IVL catheter, which can deliver up to 120 impulses per catheter, as compared to 80 impulses in earlier catheters (though not >80 impulses should be delivered to a single coronary segment). It is 5 Fr compatible and is useful in longer calcified segments and multi-vessel calcified lesions^[31] [Figures 1a-c].

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Figure 1:

Shockwave intravascular lithotripsy. (a): Baseline coronary angiogram showing severe calcified stenosis in the coronary artery. (b): IVL balloon positioned across the lesion with shockwave pulses being delivered to modify the calcified plaque. (c): Post-IVL angiogram showing improved luminal gain and vessel expansion following successful calcium modification (intravascular lithotripsy).

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IVL has a relatively short learning curve and can be used alone or in a combination with other calcium ablative or modifying techniques. IVL uses acoustic shockwaves delivered at lower pressure, reducing the risk of vascular complications and causing fractures in both superficial and deep calcium, which improves vessel compliance. It can be used on work horse wire, without any risk of debris or distal embolization. Although IVL is especially useful in circumferential calcium, calcium arc >270, but now there is increasing evidence about its usefulness in eccentric and nodular calcium also.^[25] EMPOWER CAD study, ongoing study is focusing solely on female patients, to emphasize the safety and efficiency of IVL in complex coronary cases in women.^[32]

In 2021, IVL received food and drug administration (FDA) approval for use in calcified coronary lesions following the DISRUPT II and III trials. IVL plays a key role in treating calcified coronary lesions in current clinical practice. The DISRUPT CAD trials demonstrated that IVL significantly improves luminal gain and stent expansion rates in calcified coronary lesions, providing better procedural outcomes and enhanced stent deployment compared to traditional methods. It can also be successfully used for acutely implanted underdeployed stent.^[33]

ABLATIVE TECHNIQUES

Despite development of newer technologies, there are lesions which cannot be crossed or expanded with conventional or advanced balloons (balloon non-crossable lesions) and need lesion atherectomy before any other therapy.

Rotational atherectomy (Rotablator) was the first calcium ablative system and has been available since 1993. Rotablator consists of a half diamond coated burr which works on differential cutting technology, while rotating at speed of 135,000–180,000 rpm. The recommended burr size to the reference vessel diameter is 0.4–0.6. The rota burr are available in sizes 1.25–2.5 mm, which are compatible with 6–8 Fr guide catheter.^[34] Rota catheter is advanced on a dedicated 0.009” RotaWire which tapers to 0.005” and then terminates in 0.014” spring tip. RotaWires are available in two types – RoAT floppy and rota extra support. In the PREPARE-CALC trial, (Prepare severely calcified coronary lesion trial) rota was demonstrated to be superior to conventional PCI with higher procedural success and superior stent expansion while using rota.^[35] ACC/AHA/SCAI 2021 guidelines have given class II a recommendation for rotational atherectomy in severely calcified lesion [Figures 2a-c].

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Figure 2:

Rotational atherectomy. (a): Baseline angiogram showing heavily calcified lesion in the coronary artery. (b): Rotational atherectomy burr being advanced across the lesion for plaque modification. (c): Post-atherectomy angiogram demonstrating improved vessel lumen with successful calcium debulking.

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Rota-Pro (Boston scientific) is a newer advancement in rotational atherectomy. It is single operator friendly device (as compared to conventional rota), and has all controls on the table top along with the advancer, eliminating the need for foot pedals and is likely to have better penetration for use in calcified non-crossable coronary lesions.

OA

OA is a newer technology for calcium modification. It works on the principle which is based on centrifugal force and differential sanding. DIAMOND BACK 360 orbital atherectomy system (OAS) has a standard 1.25 mm eccentrically mounted diamond coated crown, mounted 6 mm from the tip (nosecone), which does sanding as well as ablation while having eccentric rotation when in use. It is used on a dedicated 0.012 wire (viper wire) with 0.014 tip which is relatively easy to maneuver as compared to RotaWire. It works both in forward and backward directions, bidirectional atherectomy, as opposed to only forward atherectomy achieved with rota burr. The lumen size achieved depends on the rotational speed and speed of the crown advancement, with better results with slower advancement of the crown, 1.0 mm/s, with both forward and backward movements [Figures 3a-c].^[36-38]

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Figure 3:

Orbital atherectomy. (a): Coronary angiogram showing a calcified lesion in the right coronary artery (RCA). (b): Orbital atherectomy device positioned at the lesion site to facilitate rotational plaque modification using centrifugal force. (c): Post-procedural angiogram displaying improved vessel patency and luminal gain following successful orbital atherectomy.

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The intimal calcium is reduced to smaller particles, around 2 microns (compared to 5–10 microns with rotational atherectomy), which helps minimize the risk of slow flow or no re-flow. Vessels ranging from 2.5 to 4 mm in size can be treated with a single crown, compatible with a 6 Fr guiding catheter. The safety and efficacy of OA have been established through the ORBIT I and ORBIT II trials, as well as multiple studies conducted thereafter [Table 1].^[39]

ACC/AHA/SCAI 2021 guidelines recommend OA as IIb recommendation for treatment of heavily calcified coronary lesions.

Rotational and OA are techniques for treating calcified coronary lesions, each with distinct use and clinical outcomes. Rotational atherectomy uses a high-speed, diamond-coated burr to grind away plaque, offering high procedural success but with a relatively higher risk of complications, such as vessel perforation and slow/no reflow. OA employs a rotating crown to create controlled lesions, resulting in better stent expansion and a lower complication rate, including reduced risk of slow flow [Table 1].

TREATMENT ALGORITHMS

The 2021 ACC/AHA/SCAI guidelines recommend using intracoronary imaging for guiding procedures in complex calcified coronary lesions (class IIa). Recent 2025 ACC/AHA/SCAI guidelines for ACS have upgraded the intracoronary imaging to class I now.

ACC/AHA algorithms assess the calcium arc, plaque depth, length, and minimal luminal area, all of which require intravascular imaging. If the imaging catheter cannot pass, athero-ablative techniques are needed. After plaque modification, intracoronary imaging should confirm the results before proceeding with stenting^[51-54] [Figure 4].

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Figure 4:

Calcium modification. (OCT: Optical coherence tomography, IVUS: Intravascular Ultrasound, NC: Non-compliant, CB: Cutting balloon, IVL: Intravascular lithotripsy).

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CONCLUSION

Severe coronary calcified lesions pose a significant challenge during PTCA. These lesions are associated with increased periprocedural complications and suboptimal results as compared to non-calcified lesions. Identification of presence and extent of calcium and assessing the treatment effects on the plaque, using intracoronary imaging is the key to guide a suitable calcium modification strategy for procedure. Recent technological developments in the form of better imaging and treatment modalities are likely to help interventional cardiologists to treat this challenging subset of lesions with better periprocedural and long-term outcomes.