Review

Solving Challenging Situations and Complications in Everyday Percutaneous Coronary Intervention Using Chronic Total Occlusion Techniques

Lorenzo Azzalini, MD, PhD, MSc1,2 *; Georgios Tzanis, MD, PhD1*; Kambis Mashayekhi, MD3; Barry F. Uretsky, MD4; Soledad Ojeda, MD, PhD5; Manuel Pan, MD, PhD5; Stephane Rinfret, MD, MS6; Alexandre Avran, MD7; Khaldoon Alaswad, MD8; Masahisa Yamane, MD9; Dimitri Karmpaliotis, MD, PhD10; Emmanouil S. Brilakis, MD, PhD11; Mauro Carlino, MD1; Luiz F. Ybarra, MD, PhD, MBA12

Lorenzo Azzalini, MD, PhD, MSc1,2 *; Georgios Tzanis, MD, PhD1*; Kambis Mashayekhi, MD3; Barry F. Uretsky, MD4; Soledad Ojeda, MD, PhD5; Manuel Pan, MD, PhD5; Stephane Rinfret, MD, MS6; Alexandre Avran, MD7; Khaldoon Alaswad, MD8; Masahisa Yamane, MD9; Dimitri Karmpaliotis, MD, PhD10; Emmanouil S. Brilakis, MD, PhD11; Mauro Carlino, MD1; Luiz F. Ybarra, MD, PhD, MBA12

Abstract: The field of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has witnessed a dramatic evolution in the last decade. The challenging nature of CTO interventions involves regularly dealing with support-related issues, uncrossable/undilatable lesions, manipulation of equipment in the subadventitial (also known as “subintimal”) space, and the treatment of complications such as perforation and equipment loss or entrapment. The CTO experience has provided numerous techniques to the creative operator facing challenges in the non-CTO PCI setting. Herewith, we discuss an armamentarium of techniques routinely used in CTO-PCI, which can also be utilized in interventions for non-occlusive coronary artery disease and have the potential to improve the efficacy and safety of these procedures.

J INVASIVE CARDIOL 2020;32(3):E63-E72.

Key words: chronic total occlusion, complications, occlusion, percutaneous coronary intervention, perforation, rupture


Percutaneous coronary intervention (PCI) has undergone tremendous development over the last decade. These advancements have allowed a remarkable expansion in the lesions amenable to PCI, which has particularly benefited the field of chronic total occlusion (CTO) intervention. CTO operators routinely encounter procedural challenges, such as device-uncrossable/undilatable lesions and support-related issues, manipulation of devices in the subadventitial (also known as “subintimal”) space, and the treatment of complications such as coronary perforation and equipment loss or entrapment. Although many CTO techniques are specific to the CTO setting, some can also be utilized in non-CTO interventions to address challenging situations and complications. In this article, we will review several of these techniques (Figure 1).

Problem #1: Acute Vessel Closure

Acute vessel closure can be iatrogenic or spontaneous. The main causes of abrupt vessel closure during PCI are dissection and acute stent thrombosis. Since the management of the latter involves medical therapy and standard PCI techniques, here we will focus only on techniques aimed at solving the former. 

Dissection can be caused by a variety of mechanisms, most frequently guide-catheter induced ostial injury, balloon dilation, aggressive wire manipulation, and use of atherectomy devices. The ultimate goal in this scenario is to restore coronary flow by stenting. This is easily achieved if a guidewire is already present in the distal true lumen, but can be extremely challenging if distal wire control has been lost. Antegrade contrast injections should be avoided to minimize propagation of the dissection. Sometimes, a workhorse guidewire can be advanced through the dissection plane into the true lumen, followed by stenting. If this fails, several CTO-PCI techniques (outlined below) can be attempted. If those are unsuccessful, emergency coronary artery bypass grafting (CABG) can be considered as a last resort for cases with hemodynamic instability and severe ischemia.

Advanced wiring techniques. In case of vessel dissection where true lumen wiring with workhorse wires has failed, CTO guidewires (with intermediate or high tip-load) can be used to re-enter the distal true lumen. Such wires can be advanced over a dual-lumen microcatheter to facilitate their delivery and enhance wire manipulation (Figure 2). This strategy is particularly useful in cases of side-branch loss during bifurcation intervention, where a certain degree of tip stiffness is required to steer through the stent struts and dissection planes.

Intravascular ultrasound (IVUS)-guided re-entry. IVUS-guided re-entry is another option to deal with acute vessel closure (Figure 3), and can indeed be very effective, provided that significant expertise with IVUS interpretation exists. The IVUS probe is advanced into the subadventitial space of the dissected vessel. A second guide can be engaged into the same coronary ostium (the “ping-pong” technique; described below), and a guidewire, supported by a microcatheter, can be carefully advanced into the true lumen under live IVUS guidance. Alternatively, this maneuver can be performed via a single 8 Fr guide.

Dissection/re-entry strategies. (1) The Stingray system. Based on CTO experience, following inadvertent or intentional crossing into the subadventitial space, re-entry into the distal true lumen can be achieved using the Stingray system (Boston Scientific).1 Stingray is a low-profile balloon that has a flat shape with two exit ports for re-entry, and a distal port for balloon delivery at the re-entry zone. After low-pressure inflation, Stingray self-orients, wrapping around the vessel. A dedicated, stiff wire with a distal tip prong to “poke” through the tissue (Stingray guidewire) or another CTO high tip-load wire is then directed toward the side port of the Stingray balloon facing the true lumen, to achieve re-entry.2 

Stingray-based re-entry can be successfully applied in non-CTO scenarios, specifically in the context of acute vessel closure (Figure 4). Martinez-Rumayor et al3 first reported a case of iatrogenic occlusive coronary dissection where distal true lumen control had been lost. The operator safely advanced a knuckle wire in the subadventitial space, and then successfully performed Stingray-based re-entry distal to the dissection entry point.

(2) Antegrade fenestration and re-entry (AFR). In 2018, Carlino and Azzalini introduced a novel re-entry technique for CTO-PCI called “antegrade fenestration and re-entry.”4 The AFR technique creates multiple fenestrations in the dissection flap separating the false and true lumen. In AFR, a guidewire is advanced antegradely in the subadventitial space beyond the distal cap of the occlusion. A second low tip-load polymer-jacketed guidewire is then brought in close proximity with the first one, with its tip just proximal to the distal cap. A balloon, sized 1:1 with the artery, is subsequently advanced onto the first guidewire and inflated at nominal pressure, at the level of the distal cap. This maneuver creates transient fenestrations between the false and true lumen, which can be effectively engaged with the second guidewire, thus achieving re-entry (Figure 5). The versatility of AFR has recently been demonstrated by Merella et al,5 who successfully utilized this approach to treat a case of iatrogenic occlusive coronary dissection during primary PCI.

(3) Subintimal tracking and re-entry (STAR). STAR was the first subadventitial technique for CTO-PCI.2 A subadventitial cleavage plane is created by advancing a polymer-jacketed wire with a J-loop configuration at its tip (“knuckle”) to achieve a blunt dissection along the vessel architecture, until it spontaneously re-enters into the distal true lumen. Contrast-guided STAR represented an evolution of the original technique. With this variation, a small amount of contrast (2-3 mL) is forcefully injected through a microcatheter into the subadventitial space to achieve hydraulic recanalization of the vessel.2 

STAR has also been successfully utilized to achieve true lumen re-entry in cases of abrupt vessel closure in non-CTO-PCI (Figure 6). Carlino et al6 described a series of 11 patients who suffered iatrogenic occlusive coronary dissection. In all cases, true lumen re-entry was achieved with the STAR or contrast-guided STAR techniques. Angiographic success was achieved in all patients. However, similar to STAR in the context of CTO-PCI, this “rescue STAR” technique also has the disadvantage of an unpredictable site of re-entry, creation of extensive dissections, possible side-branch loss, and suboptimal run-off, which have been linked to higher rates of restenosis on follow-up.2

(4) Retrograde approach. In case of abrupt vessel closure, collateral channels can develop within minutes, and can be taken advantage of to allow retrograde crossing of the acute occlusion (Figure 7). Okumura et al7 reported a case of an obstructive coronary dissection of the right coronary artery (RCA) following blunt chest trauma. After antegrade wiring attempts failed, the authors accessed the occluded RCA via septal collaterals from the left anterior descending (LAD), utilizing a CTO guidewire and microcatheter. When the antegrade guide catheter was engaged by the retrograde wire and microcatheter, a 330 cm externalization wire was used to create a rail across the retrograde and antegrade system, followed by stent implantation and restoration of antegrade flow.

Problem #2: Equipment Loss

Equipment loss is an infrequent (<0.5%) but potentially life-threatening complication during non-CTO PCI, as it may cause stent thrombosis, myocardial infarction, and death.8 For a comprehensive review of all available techniques to deal with device loss (small-balloon technique, crushing, extraction with biopsy forceps, etc) the reader is referred to specific literature.9 Here, we will describe only snaring, which is a technique commonly performed by CTO-PCI operators during the externalization step of the retrograde approach.1 While big snares are usually employed in non-coronary vessels, small snares (<5 mm) are also available and can be advanced into the coronary arteries to retrieve lost equipment (stents, balloons, atherectomy devices, etc). There are several microsnare types available (gooseneck vs three-loop), consisting of a wire loop typically made of nitinol that is advanced and then positioned around the lost device. The easiest way to get the snare into the coronary artery is to put the loop of the snare around a guidewire (ideally the very guidewire that delivered the lost device) and use it as a track for the snare. When pulled back, the snare facilitates trapping of the lost device within the catheter. The snare is then removed together with the lost device. Maintaining continuous traction prevents losing the catch of the captured device and allows safe retrieval of the entire system. 

Problem #3: Entrapped Rotational Atherectomy Burr

Entrapment of the burr within the calcified lesion is an infrequent but serious complication of rotational atherectomy. This typically happens when the burr is pushed forcefully through the calcified segment without achieving effective plaque modification, and is preceded by marked deceleration of the burr. To reduce the risk of burr entrapment, slow pecking motions are recommended in order to minimize the decelerations.1 Besides surgical removal of the entrapped burr, specific percutaneous bail-out techniques have been proposed. 

The simplest option is represented by deep guide-catheter intubation, with subsequent forceful pull of the entire system. Another possibility is to cut the Rotablator drive shaft sheath, catheter shaft, and Rotawire (Boston Scientific), and remove the drive shaft sheath, to allow passage of a second guidewire and a balloon catheter inside the same guide catheter. The new guidewire is then advanced distal to the entrapped burr and balloon inflations around the entrapped burr are performed to free it.10 Chiang et al11 reported two successful burr retrievals by using a guide-catheter extension with and without the combination of a microsnare. With this technique, the drive sheath and the Rotablator catheter should be cut off, and then the guide-catheter extension is advanced through the remnant of the Rotablator system. Its tip is advanced as close as possible to the entrapped burr. A simultaneous maneuver of pulling the Rotablator system and pushing the guide-catheter extension can release the trapped burr. If this is unsuccessful, a 4 mm snare should be advanced through the guide-catheter extension and opened at the entrapment site. Then, the aforementioned pull-push maneuver might free the burr. 

Another technique involves crossing the site of entrapment with a second guidewire in a subadventitial fashion, and then re-entering into the distal true lumen with the STAR technique. This is followed by advancement of a small balloon onto this guidewire, and inflation to dislodge the trapped burr (Figure 8).12

Problem #4: Coronary Perforation

Coronary perforation is very frequent in CTO-PCI (5.5%),13 and it is not surprising that current state-of-the-art coronary perforation management strategies are deeply influenced by techniques developed and employed by CTO operators. Achieving immediate hemostasis is the initial goal, and this can be easily obtained by low-pressure balloon inflation immediately proximal to the perforation site. Prolonged balloon inflation is sometimes able to stop minor wire-induced perforations, although a more definitive treatment is often required to deal with perforations induced by other devices (balloons, stents, atherectomy devices, etc) or major wire-induced perforations. In such cases, a second vascular access should be secured and a second guide catheter is then advanced. The two guide catheters will alternatively engage the coronary ostium, to perform key maneuvers meant to seal the perforation while minimizing the time in which bleeding into the pericardium occurs (the “ping-pong” technique, Figure 9). If bleeding has not stopped after some minutes of balloon inflation, advancement of a second guidewire distal to the perforation site from the second guide catheter should be performed, deflating the balloon loaded onto the first guide catheter only for a few seconds. The subsequent management depends on the specific site of perforation. If the latter involved a major vessel, then covered stent implantation should be performed via the second guide catheter (Figure 9). If it is a case of small-vessel perforation, coil embolization should be performed with a microcatheter via the second guide (Figure 10). Alternatives to coils are microspheres, thrombin, medical glue, or subcutaneous fat. Perforated distal side branches can be also managed by exclusion with covered stent implantation in the main vessel. An alternative to the ping-pong technique is the single guide-catheter approach. This is particularly appealing if the guide that was chosen for PCI is 7 or 8 Fr, as such catheters can fit multiple devices needed for coronary perforation management (two wires, one balloon, and one microcatheter for coil embolization, or one covered stent). Heparin reversal with protamine is not routinely recommended, particularly until all gear has been removed and pericardial effusion has been drained, to avoid the risk of intracoronary and intrapericardial thrombosis, respectively.

Problem #5: Lack of Support and 

Device-Uncrossable/Undilatable Lesions

Balloon-uncrossable/balloon-undilatable lesions are encountered in 9% of CTO-PCIs and are associated with significantly lower procedural success rates.14 However, they are also common in non-CTO PCIs. Two main approaches can address this problem: (1) increasing support and (2) modifying the plaque. Combining the two approaches might lead to optimal results. 

(1) Increasing support. Adequate guide support is a prerequisite when dealing with uncrossable lesions. The techniques/maneuvers to increase guide-catheter support are: 

(a) Supportive guide catheters (for passive support). Guide catheters with larger diameter and/or tip size (for a given diameter of the aorta) as well as more aggressive guide shapes (eg, Amplatz), routinely employed in CTO-PCI, will increase passive support.15 Also, the femoral approach offers more support compared with the radial route, and might sometimes be sufficient to deal with support-related issues.

(b) Deep guide-catheter intubation (for active support). Deep guide-catheter intubation increases active support but carries a certain risk of dissection.15 The guide should be advanced coaxially with gentle rotation over the rail provided by the guidewire (with/without a balloon), to decrease the risk of vessel wall damage (Figure 11A). This is especially useful and reasonably safe for the RCA, but less so for the left coronary, as impaired flow into the circumflex (if deep intubation is performed into the LAD, or vice versa) might arise with the untoward effects of prolonged ischemia. 

(c) Guide-catheter extensions. A guide-catheter extension provides a major increase in support.15 The guide-catheter extension can be advanced in the vessel with the distal anchor technique (also known as the “inchworm” technique),16 in which a balloon is inflated distal to the guide-catheter extension tip to anchor the latter and facilitate its advancement, with a decreased risk of vessel trauma compared with passage of the extender over the wire alone (Figure 11B).

Some challenging cases of PCI through long and tortuous bypass grafts can utilize the “mother-daughter-granddaughter” technique, in which a 6 Fr guide-catheter extension is inserted into an 8 Fr guide-catheter extension, and the ensemble is advanced through the tortuous graft and retroflexed angle of the native coronary artery, thus maximizing support and allowing delivery of balloons and stents.17 

(d) Buddy wire. Use of a supportive “buddy” wire deep in the vessel or in a side branch is an easy and simple technique to provide extra support.

(e) Anchoring techniques. The anchoring technique utilizes a balloon that is inflated on a wire placed in a side branch proximal to the target lesion, with the intent to anchor the guide catheter and facilitate the advancement of balloons or stents toward the target lesion (side-branch anchoring, Figure 11C). With co-axial anchoring, the balloon is inflated in the coronary artery proximal to the occlusion, to facilitate at least partial advancement of the gear toward the lesion. With distal anchoring, the balloon is inflated distal to the lesion site of the target artery. 

(f) Retrograde approach via bypass grafts. The retrograde approach can be used to facilitate the treatment of very tortuous non-CTO lesions in post-CABG patients. In 1990, Kahn and Hartzler18 first described retrograde access through saphenous vein grafts (SVGs) of 17 patients to dilate stenoses of the native arterial segments proximal to the SVG anastomosis site. Recently, Siraj et al19 utilized the retrograde approach through the patent jump limb of an ostially occluded SVG to recanalize a tortuous bifurcation lesion in the circumflex system.

(2) Plaque modification. Plaque modification can be performed with balloons, microcatheters, atherectomy devices, and advanced subadventitial techniques adopted from CTO-PCI.

(a) Low-profile balloons. The first step is to advance a small diameter (<1.5 mm) semicompliant balloon. After crossing of the lesion and successful dilation, progressively larger-diameter and larger-profile balloons can be utilized. 

(b) Balloon-assisted microdissection (BAM). The BAM technique20 is a CTO-PCI technique in which, after successful guidewire crossing, a small-profile balloon is advanced as distal as possible inside the lesion and then inflated at high pressure until it ruptures. The sudden increase in local pressure (barotrauma) caused by balloon rupture can modify the plaque, resulting in successful crossing with a new balloon. 

(c) The wire-cutting technique. The wire-cutting technique is applied after two guidewires are advanced distal to the lesion and a balloon is then advanced over one guidewire and placed as distal as possible into the uncrossable lesion. The balloon is then inflated in order to compress the buddy wire on the lesion, producing a scoring effect that can modify the plaque and facilitate further balloon advancement.1 After deflation and removal of this balloon, a new balloon is advanced, successfully crossing the lesion. A modified wire-cutting technique is the seesaw balloon-wire cutting technique,21 where after advancement of two guidewires into the distal lumen, two short and low-profile balloons are advanced simultaneously over the guidewires. The two balloons are alternatively advanced and inflated until the lesion is adequately modified and crossed.  

(d) Microcatheters. The rationale behind using microcatheters for a balloon-uncrossable lesion is their very low crossing profile and the fact that they can modify plaque geometry and compliance with their transit, enabling subsequent crossing with a small balloon.1 This is usually achieved with dedicated CTO tapered-tip microcatheters, such as the Corsair Pro and Caravel (Asahi Intecc) and the Turnpike family (Teleflex). Moreover, there are microcatheters that have been specifically designed for balloon-uncrossable lesions, such as Tornus (Asahi Intecc) and Turnpike Gold. 

(e) Atherectomy. Atherectomy can effectively provide plaque modification by means of the interaction of the burr (rotational), crown (orbital), or laser energy with the resistant fibrocalcific tissue.22 With rotational atherectomy, differential cutting of the calcified lesion is provided by the diamond-coated burr. Orbital atherectomy achieves plaque modification by means of “sanding” with progressively larger orbital movements. The mechanism of plaque modification of laser atherectomy is photothermal ablation. 

(f) Advanced subadventitial techniques. In cases of a balloon-uncrossable lesion, a second guidewire is used to enter the subadventitial space, reaching a position slightly more distal to the uncrossable lesion. The lesion can then be crushed by balloon inflation onto this subadventitial wire, modifying plaque geometry from outside with an “external crush” technique (Figure 12A).23 Alternatively, if the subadventitial wire has been advanced in a knuckle fashion, this alone can be sufficient to achieve plaque modification.24 Another option is represented by the subadventitial distal anchor, in which a guidewire is advanced subadventitially, distal to the uncrossable lesion, and then a balloon is inflated distally, effectively anchoring the system so that antegrade delivery of a second balloon can be achieved onto the wire that initially crossed the lesion (Figure 12B).25 

Problem #6: Extraction and Insertion of Over-the-Wire Catheters Over Conventional Guidewires

Some techniques that are frequently used in CTO interventions for removing or inserting an over-the-wire system (eg, microcatheters) when using a conventional (180-190 cm) guidewire can also be applied in non-CTO PCIs. 

(a) Trapping. Guidewire displacement during microcatheter exchange can potentially result in guidewire position loss, distal vessel injury, and/or perforation. Trapping is the best technique for removing or inserting microcatheters or any over-the-wire system when using a 180-190 cm guidewire, as it ensures minimal guidewire displacement compared with the use of guidewire extensions.1 With trapping, a balloon (2.0 mm for 6 Fr guide catheters; 2.5 mm for 7 Fr and 8 Fr guides) is advanced freely (ie, not onto a wire) into the guide catheter, distal to the position where the device to be extracted is located (the latter has to be previously pulled inside the catheter as proximal as possible). Balloon inflation “pins” the guidewire against the catheter wall, thus preventing its movement (Figure 13).1 Another scenario where this technique can be applied is during workhorse wire exchange with the Rotawire in preparation for rotational atherectomy. 

(b) Nanto technique. With the Nanto technique (also called hydraulic exchange),26 the indeflator is connected to the guidewire lumen of the microcatheter after pulling back the latter until the proximal end of the guidewire is at the hub level. The microcatheter is further pulled back while applying constant inflation pressure with the indeflator, leaving the guidewire in the coronary artery. The Nanto technique is easier to perform than trapping, but also less reliable in maintaining distal guidewire position. 

(c) Use of a guidewire extension. Use of a guidewire extension can be performed by inserting the back end of the guidewire into the extension guidewire in order to remove a microcatheter used during the procedure. However, each guidewire brand requires a specific extension, and extraction with this system takes longer and sometimes fails in maintaining distal wire position. 

Problem #7: Crossing Difficult Lesions

Selecting the right guidewire can facilitate successful crossing of difficult lesions. In a coronary subocclusion, tapered-tip guidewires should be avoided, as these can easily dissect into the subadventitial space. Instead, a low tip-load non-tapered-tip hydrophilic guidewire should be used. Once the lesion is crossed, this guidewire should be exchanged for a safer workhorse guidewire to avoid injury to the distal vessel. Moreover, keeping the guidewire tip knuckled can increase its safety by decreasing the chance of tip perforation.

The guidewire tip should ideally not be preshaped; the tip should be bent according to the lesion and the need. In coronary subocclusions, a CTO-type tip (1 mm, 45°) works better than others as it can easily engage the lesion and safely navigate through it. 

Conclusions

The experience gained in the field of CTO-PCI can provide numerous techniques for the creative operator facing challenges in the setting of non-CTO PCI. Mastering these techniques may significantly improve the procedural efficiency and safety of non-CTO PCI. 


*Joint first authors.

From the 1Interventional Cardiology Division, Cardio-Thoracic-Vascular Department, San Raffaele Scientific Institute, Milan, Italy; 2Cardiac Catheterization Laboratory, The Mount Sinai Hospital, New York, New York; 3Division of Cardiology and Angiology II, University Heart Center Freiburg, Bad Krozingen, Germany; 4Division of Cardiology, Central Arkansas Veterans Health System, University of Arkansas for Medical Sciences, Little Rock, Arkansas; 5Division of Interventional Cardiology, Reina Sofia Hospital, University of Cordoba, Maimonides Institute for Research in Biomedicine of Córdoba (IMIBIC), Cordoba, Spain; 6Interventional Cardiology, McGill University Health Centre, Montreal, Quebec, Canada; 7Clinique Saint Georges, Nice, France; 8Cardiac Catheterization Laboratory, Edith and Benson Ford Heart and Vascular Institute, Henry Ford Hospital, Detroit, Michigan; 9Cardiology Department, Saitama Sekishinkai Hospital, Saitama, Japan; 10Center for Interventional Vascular Therapy, Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, New York; 11Center for Advanced Coronary Interventions, Minneapolis Heart Institute and Minneapolis Heart Institute Foundation, Minneapolis, Minnesota; and 12London Health Sciences Centre, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Tzanis reports funding from the European Society of Cardiology (ESC) in the form of an ESC training grant. Dr Azzalini reports honoraria from Abbott Vascular, Guerbet, Terumo, and Sahajanand Medical Technologies; research support from ACIST Medical Systems, Guerbet, and Terumo. Dr Mashayekhi reports consulting, speaker, and/or proctoring honoraria from Abbott Vascular, Asahi Intecc, AstraZeneca, Biotronik, Boston Scientific, Cardinal Health, Daiichi Sankyo, Guerbet, Medtronic, SIS Medical, Teleflex, Terumo. Dr Uretsky reports research support from Nitiloop. Dr Rinfret reports consultant honoraria from Boston Scientific, Teleflex, Abbott Vascular, Abiomed, and SoundBite Medical. Dr Avran reports proctoring income from Boston Scientific, Abbott Vascular, Terumo, Biotronik, and Biosensors. Dr Alaswad reports consulting honoraria from Cardiovascular Systems, Abbott Vascular, Boston Scientific, and LevaNova. Dr Karmpaliotis reports honoraria from Abbott Vascular, Boston Scientific, and Medtronic. Dr Brilakis reports consulting/speaker honoraria from Abbott Vascular, American Heart Association (associate editor, Circulation), Biotronik, Boston Scientific, Cardiovascular Innovations Foundation (Board of Directors), CSI, Elsevier, InfraRedx, GE Healthcare, Siemens, Teleflex, and Medtronic; research support from Siemens, Regeneron, and Osprey; shareholder in MHI Ventures. The remaining authors report no conflicts of interest regarding the content herein.

Manuscript submitted September 23, 2019, version accepted October 2, 2019.

Address for correspondence: Lorenzo Azzalini, MD, PhD, MSc, Interventional Cardiology Division, Cardio-Thoracic-Vascular Department, San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy. Email: azzalini.lorenzo@hsr.it

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