Vascular access is an essential part of all interventional procedures whether coronary or structural. Over the last 15 to 20 years, in coronary interventions, traditional femoral access has been mostly replaced by the radial approach. Nonetheless, the femoral approach through both artery and vein is still the main approach for structural heart procedures. Over the last few years, femoral access has evolved from a puncture guided by anatomical references to more accurate ultrasound-guided approaches. The relatively recent introduction of interventions such as transcatheter aortic valve replacement has conditioned the use of large introducers and ultimately the need for specific hemostatic systems, above all, percutaneous closure devices. This manuscript reviews different anatomical concepts, puncture techniques, diagnostic assessments, and closure strategies of the main arterial and venous approaches for the diagnosis and treatment of different structural heart procedures.

Keywords: TAVI. Vascular. Accesses. Structural.


El acceso vascular es una parte esencial de cualquier procedimiento intervencionista coronario o estructural. En procedimientos coronarios, el acceso femoral tradicional prácticamente ha sido sustituido por el radial desde hace 15-20 años. No obstante, el acceso femoral, tanto arterial como venoso, sigue siendo la principal vía de abordaje para el intervencionismo estructural. El acceso femoral ha ido evolucionando con el paso del tiempo de una punción mediante referencias anatómicas a una punción mucho más precisa guiada por ecografía. La llegada de técnicas como el recambio valvular aórtico percutáneo ha condicionado el uso de introductores arteriales de gran tamaño y, por tanto, la necesidad de sistemas de control de la hemostasia, principalmente los sistemas percutáneos de cierre vascular. Este artículo revisa diversos conceptos anatómicos, técnicas de punción, evaluación diagnóstica y estrategias de cierre de las principales vías de acceso arterial y venoso utilizadas en el diagnóstico y el tratamiento de diferentes patologías estructurales.

Palabras clave: TAVI. Vascular. Accesos. Estructural.

Abbreviations CFA: common femoral artery. PDA: patent ductus arteriosus. TAVI: transcatheter aortic valve implantation.


Arterial puncture technique

Vascular access is an essential part of all interventional procedures whether coronary or structural. Over the last 15 to 20 years, traditional femoral access has been replaced by the radial approach in coronary interventions. However, the femoral approach is still the most widely used regarding structural hear procedures. Brachial, cubital, axillary or carotid accesses are also used, but to a lesser extent. Knowledge of anatomy and the puncture technique is essential. This is particularly relevant in accesses different from the radial/cubital one where the rate of complications is higher especially if large catheters and devices are used.

Femoral artery access

Common femoral artery (CFA) is the best puncture site because of its larger size and location on the femoral head favoring its palpation and compression view. The CFA is in the lateral femoral sheath, the common femoral vein is in the medial sheath while the femoral nerve rests outside the sheath, lateral to the artery. Distally, it can be divided into superficial and deep femoral arteries. High punctures above the inguinal ligament complicate arterial compression and trigger possible retroperitoneal bleeding. Low punctures in the superficial or deep femoral artery, however, increase the chances of pseudoaneurysm, hematoma or ischemia and arteriovenous fistula because, at that level, the vein and the artery often overlap, and can be crossed inadvertently.

There are 3 basic ways to catheterize the CFA:

1) Skin-based punctures

The most widely used in the past. Typically, here we’d be palpating the arterial beat 2-to-3 cm underneath the inguinal skin fold. Local anesthesia is administered followed by a needle using the modified Seldinger technique. Then, the anterior wall is punctured to prevent bleeding into the artery posterior region. Once pulsatile flow is obtained, the guidewire is inserted towards the abdominal aorta under fluoroscopy guidance. Alternatively, a micropuncture system can be used to open a smaller orifice (almost 60% smaller) with the potential to minimize complications. Afterwards, a 0.018 in guidewire is used followed by a 4-Fr introducer sheath through which a 0.035 in guidewire can be inserted. Skin-based punctures are not optimal if accuracy is what we’re after.

2) Based on radiographic references

The femoral head is seen on the fluoroscopy and a radiopaque marker is placed in its inferior border as a height reference. If punctured with an inclined needle between 30º to 45°, this becomes be the perfect spot to insert the needle and try to pinch the artery halfway through the femoral head (figure 1). If punctured a little more vertically, the skin should be accessed a little more cranially. Inguinal ligament is often found 15 mm above the medial femoral head. In most patients, femoral artery bifurcations can often be found distal to the femoral head inferior side. That’s why the medial femoral head is the target here. If large caliber introducer sheaths should be needed like for transcatheter aortic valve implantation (TAVI), a variation of this technique should be used and contrast injected through an advanced catheter via a different arterial access towards the CFA to spot it correctly.

Figure 1. Radiographic references of punctures on the femoral artery.

3) Ultrasound-guided

Most interventional cardiologists trained over the last 15 years have limited experience with the femoral approach following the popularity gained by the radial access. Therefore, it seems logical somehow to think that femoral access training should be based on ultrasound guidance. An 8-to-12 MHz vascular linear probe is introduced into a sterile bag. 2D echo shows the CFA directly, its bifurcation, and the femoral head. The CFA should be assessed in the long axis from its bifurcation until it later enters the pelvis by measuring its caliber and assessing the presence of atheromatous plaques. The artery should be assessed in its short or cross-sectional axis that shows the typical «Mickey mouse head» look in the arterial bifurcation with the medial vein and the superficial femoral artery on the deep femoral artery, and the entire CFA cut section to assess which section is healthier by moving the transducer cranially (video 1 of the supplementary data). The vein looks different from the artery because it is much more compressible and for the direction and velocity of flow on the color Doppler echocardiography. Ultrasound-guided assessment allows us to select the arterial region with less calcium in the anterior wall. Infiltration with a local anesthetic at this spot and ultrasound-guided puncture—that reveals the entry of the needle in the center of the artery—facilitate the proper functioning of the closure systems. After introducing the 0.035 in guidewire, the ultrasound shows that the puncture site is the proper one since the guidewire is particularly echogenic and easily visible. This approach does not require the use of contrast or x-rays during puncture. In the FAUST trial1—a prospective multicenter trial that randomized 1004 patients to fluoroscopy or ultrasound-guided femoral access for TAVI—ultrasound-guided puncture was associated with a higher rate of success in the first attempt (83% vs 46%; P < .01), fewer attempts (1.3 vs 3.0; P < .01), less risk of venous puncture (2.4 vs 15.8; P < .01), shorter mean access times (136 vs 148 seconds; P < .01), and fewer access site related complications (1.4% vs 3.6%; P = .04).

The basic complications of arterial puncture in structural heart procedures (TAVI) are shown on table 1. Old age, feminine sex, low weight or obesity, peripheral vascular disease, kidney disease, hemorrhagic diathesis, baseline anticoagulation, and introducer sheaths of a larger size are associated with more complications.2 Although the rates of vascular complications were high in the past, they have dropped significantly over the last few years.2

Table 1. Main complications of femoral artery access

Incidence rate %
Hematoma 2.2-12.5
Retroperitoneal hemorrhage 1-2.2
Iliofemoral rupture 0.7-7.1
Pseudoaneurysm 2-6
Arterial dissection 2-7.4
Local infection 1.6-6.3


Arterial closure devices were introduced for the first time at the beginning of the 1990s. For arterial accesses with > 8-Fr introducer sheaths the closure devices available are suture-mediated or bioresorbable implantation-based. Table 2 describes the 3 large caliber vascular closure devices most widely used to this date.

Table 2. Main devices for percutaneous vascular closure

Company Name Type FDA indication Characteristics
Abbot Perclose Proglide Suture-based CFA accesses (5-Fr-to-21-Fr), vein (5-Fr-to-24-Fr) Monofilament polypropylene suture with premounted knot
Minimum residual intravascular material
Keeps access guidewire
No re-access restrictions
Preclosure with 2 devices if > 8-Fr
Abbot Prostar XL Suture-based CFA accesses (8.5-Fr-to-24-Fr) 2 braided polyester sutures
4 nitinol needles
Minimum residual intravascular material
Keeps access guidewire
Preclosure if > 10-Fr
Teleflex Manta Bioresorbable implantation CFA accesses 10-Fr to-20-Fr devices No need for preclosure
Residual intravascular anchor

CFA, common femoral artery; FDA, Food and Drug Administration.


The Perclose/Proglide (Abbott Vascular, United States) is the most widely used suture-mediated device today as it is easier to use compared to the Prostar XL. It is inserted into the artery through a 0.035 in guidewire until pulsatile blood flow is seen through the lateral port. A lever releases feet inside the lumen that are pulling the artery anterior wall while releasing needles and creating a knot. The closure of the artery ties the knot. Introducer sheaths > 8-Fr require preclosure before inserting the introducer sheath following the steps already mentioned but sparing the knot tying, a maneuver that is performed at the end of the procedure. Regarding the suture-mediated device proper tunneling of subcutaneous cellular tissue is performed to make sure that the suture knot comes down. Overall, regarding TAVI procedures, preclosure is often performed using 2 devices that are released in different orientations (usually perpendicular) that are tied when the device is eventually removed resulting in an X-shape suture on the arterial surface.


The Manta device (Teleflex, United States) is available in 2 different sizes (14-Fr and 18-Fr) for arteriotomies of 10-Fr-to-14-Fr, and 15-Fr-to-20-Fr, respectively. After pinching the artery, its depth should be measured using a specific sheath. Although its performance is better in non-calcified arteries, some operators rather use it in calcified arteries because that’s where suture-mediated closure systems work worse. Closure device is mounted on a specific introducer sheath until a click sound is heard. Afterwards, the whole kit is removed until the previously measured depth and the intraarterial anchor is released using a lever. Device is pulled until a green-yellowish color can be seen in a tension indicator and, while keeping the tension, a blue cylinder is advanced that lowers a radiopaque closure and fixes the collagen material over the arterial surface. After checking hemostasis, the guidewire is removed (usually a 0.035 in high-support guidewire) and suture is cut. The anchor is then resorbed, and metal closure is useful to pinch > 2.5 cm above or below if re-accessing the artery is required.


TAVI has revolutionized the management of severe aortic stenosis turning into the treatment of choice for a great deal of patients. In TAVI selecting this or that access route conditions the results, which is why proper planning and selection is of paramount importance.

Results from the different studies published have proven unfavorable for transthoracic compared to transfemoral accesses, which is why the latter should always be prioritized.3 Also, the ongoing technological advances made, and the operators’ increased experience have reduced the rate of major vascular complications from > 10% in the early series down to < 3% over the last few years.4

Transfemoral access


In most cases, transfemoral access can be performed completely percutaneously under superficial sedation. To guarantee success, meticulous planning through coronary computed tomography angiography (CCTA) is essential and, ideally, volumetric reconstruction and analysis using specific software. Such analysis should assess, above all, the vessel minimum diameter from femoral bifurcation until the origin of the common iliac artery. A minimum of 5.5 mm for 14-Fr devices and 6 mm to 6.5 mm for the 18-Fr ones are required. However, expert operators can use accesses of smaller diameters for the lack of calcification in the 360° of the arterial wall. Tortuosities, the presence of calcified plaques, and the quality of distal beds should also be assessed. Similarly, the entire descending aorta should be studied considering transfemoral access as an entire entity from the femoral artery until the aortic annulus. When in doubt on the actual puncture site, performing an in-situ ultrasound often helps since the size of the vessel and quality of the arterial wall can be assessed very precisely. Therefore, we can have a severely diseased vessel where the ultrasound shows the presence of an area spared for puncture and posterior percutaneous closure.

Technical aspects

The puncture site extends 1 cm above the femoral bifurcation until the origin of the epigastric artery. Distally, the ideal thing to do is to get away from the bifurcation to prevent damaging the ostium of the deep femoral artery during puncture or closure. Also, to have enough space if a bailout covered stent should eventually be implanted. Proximally, puncture limit is set by the epigastric artery that—on its way down towards the anterior rectum muscle—marks the outside of the abdomen.

Ultrasound-guided puncture reduces the number of complicatios.1 The common femoral artery should be screened to select the segment with the lowest degree of calcification and smallest plaque especially in the anterior wall. The presence of anterior extensive calcification and eccentric plaques immediately proximal to the puncture site can be significant limitations to suture-mediated closure devices; in these cases, surgical approach can be considered (figure 2). Other alternatives like micropuncture or placing a pigtail catheter at the puncture site via contralateral femoral access are less common. Some centers place a safety guidewire anterogradely from the radial artery or via contralateral femoral access to perform an emergency occlusion with a balloon or implant a covered stent if closure fails; in these cases, balance between the potential benefit of the safety guidewire and the risk of vascular complications associated with a secondary femoral access should be observed.

Figure 2. Pull down of Teflon pledgets through a suture of the Proglide device.

If femoral access is achieved successfully, but there is stenosis at a more proximal level (external or common iliac artery) successive dilatations using sheaths of growing sizes or balloon dilatations can be considered. In some cases, intravascular lithotripsy can be useful. In the presence of severe tortuosities, a very high-support guidewire can be used (Lunderquist, Cook Medical, United States).

The 3 most common closure modalities are a) 2 suture-based closure devices (Proglide) in a twirl motion (one at the 11 o’clock position and the other one at the 1 o’clock position); b) 1 suture-mediate device and 1 collagen device (AngioSeal, Terumo, Japan); and c) 1 collagen closure device (Manta). The use of suture-mediated closure devices has a greater learning curve. However, it is associated with fewer serious complications or open bailout surgeries. Occasionally, more than 2 devices for complete closure are required.5 If closure system fails—with suture—keeping the guidewire inside the artery facilitates placing new devices (1 or several Proglide devices with different rotation or a new collagen-based device). If the early failing device is a collagen-based device and a bailout parallel guidewire hasn’t been left in place we won’t have a guidewire meaning that the fastest solutions available will be stent-graft implantation (stent covered with a membrane to prevent bleeding) or a call to the surgery unit for bailout surgical closure. Otherwise, in case of unfailed closure with residual bleeding, half the dose of protamine can be added followed by prolonged compression. Also, it is very effective to pull down small Teflon pledgets through the Proglide suture (figure 2). Protamine at full doses can trigger the thrombosis of the arterial system, which is why half the dose of sodium heparin administered is advised. At the end of the procedure, some operators perform control CCTAs via secondary arterial access. However, for the lack of external bleeding, the lack of complications and presence of distal flow can be confirmed on an ultrasound. Regarding secondary access for angiographies while the valve is being placed, some centers select the contralateral femoral access. However, if possible, radial access should always be prioritized since it is associated with a lower risk of bleeding and vascular complications.6

Transaxillary access

Axillary/subclavian access should not be used as the priority access in patients with good transfemoral access. Although some studies have shown good results, the Spanish registry showed a higher rate of complications compared to transfemoral access.7 Therefore, it is considered as the alternative access of choice when the transfemoral one is not good enough.

Overall, left access is the preferred one because it does not share a common origin with the carotid artery, and access looks more like the femoral one because of the greater curvature of the aorta and perpendicularity to the annular view. However, right access is barely used as it’s spared for patients with patent left internal mammary artery graft or severe stenosis of the left subclavian artery. Horizontalization of the annular view is ill-advised (> 30º to 45°) since access often occurs through the aorta lesser curvature side and is misaligned with the valve plane.

Same as it happens with transfemoral access planning using CCTA is essential to assess the presence of calcifications, stenosis, and minimum caliber, especially at the origin of the subclavian artery for being the region more prone to atherosclerosis. We should also mention the subclavian artery different histological make-up including a tunica media with more elastic fibers and a thinner adventitia layer compared to the femoral one that includes a tunica media with smooth muscle cells and a thicker and more fibrous adventitia layer.8 These characteristics turn the subclavian into a fragile artery that is more prone to ruptures or dissections. Access is often attempted using surgical techniques although percutaneous access has been reported in different series.9 The introducer sheath should not be advanced too much leaving, at least, 5 cm until the valve plane for the correct deployment of the prosthesis. In some cases, a Dacron tube graft can be sutured proximally to the artery and distally to the introducer sheath. Using the percutaneous technique, a radial-femoral loop should be created before accessing to place an occlusion balloon in case of bleeding or during the device exchange.

Transcarotid access

It’s considered as an alternative access of choice in patients without suitable transfemoral accesses in some experienced centers. Although the risk of stroke is similar to that of transfemoral approach, the main risk here is damage to peripheral nerves like the facial or recurrent laryngeal nerves—branch of the vagus nerve—complications reported in up to 2.2% of the cases.10,11

Technique that should be used here is basically surgery, and the right side is often used by performing a small 5 cm incision along the anterior border of the sternocleidomastoid muscle. Afterwards, the muscle needs to be retracted for direct exposure and puncture of the artery. Proximal clamp can be used to confirm the presence of collateral circulation and there is often continuous cerebral monitorization during the procedure. Same as it happens with subclavian access, the introducer sheath should not be advanced too much leaving enough space for the correct deployment of the valve.

Transcaval access

Transcaval access has been recently developed for alternative vascular access in percutaneous coronary interventions. Goal here is to prevent the morbidity associated with transthoracic access and add the advantages associated with venous transfemoral access (almost no complications at femoral level and the possibility of conscious sedation). However, this access requires the capacity to perform punctures from the vena cava towards the abdominal aorta through the retroperitoneum and then advance the introducer sheath and the TAVI release system. This step requires meticulous preoperative planning with CCTA. Transcaval access is feasible because the interstitial hydrostatic pressure of retroperitoneal space exceeds venous pressure, which is why the blood that comes out of the abdominal aorta during the procedure returns to venous circulation without accumulating in the retroperitoneum. On the other hand, the abdominal aorta entry zone should not have calcifications to advance the material properly and effectively close this cavoaortic shunt at the end of the procedure using an Amplatzer occluder device (often a VSD Occluder, Abbott Vascular).

The main data on transcaval access come from a multicenter, prospective registry of 100 patients.12 This registry confirmed a rate of procedural success of 99%, yet rates of potentially fatal hemorrhages and vascular complications of 7% and 13%, respectively. Therefore, to this date, its use is basically marginal.

Direct aortic surgical access

Direct aortic surgical access requires general anesthesia and was developed as an alternative to transapical access to overcome the complications and myocardial damage associated with apical access. It requires partial upper sternotomy towards the second or third right intercostal space. It is barely used today.

Particularities of arterial access in other structural heart procedures

Paravalvular leaks

Paravalvular leak closure is probably one of the most complex techniques out there and with greater heterogenicity among operators. Paravalvular leaks can be divided into aortic and mitral.

Aortic paravalvular leaks

Access is basically retrograde (aorta-ventricle). Therefore, arterial puncture is essential. In most cases, an Amplatzer Vascular Plug 3 device (AVP3) (Abbott Vascular) is implanted. These devices require introducer sheaths between 6-Fr and 7-Fr. The Amplatzer Vascular Plug 4 device is suitable for smaller leaks because it can be advanced through a 4-Fr diagnostic catheter. These procedures can be performed via radial access13 although most operators rather use the femoral artery to prevent the risk of spasm in cases where significant catheter manipulation is required. Overall, the use of a high-support guidewire in the left ventricle is enough to provide support to advance the delivery catheters. In this sense, high-support guidewires like the ones used in TAVI procedures are advised to prevent left ventricular perforations. Otherwise, the creation of an arteriovenous loop may be required and even an arterioarterial prosthetic loop (especially useful in leaks over self-expanding TAVIs).14 In both cases, additional specific venous or arterial accesses will be needed. Finally, we should mention that despite the limited size of introducer sheaths, the use of vascular closure systems is advised since we’re mostly dealing with patients with mechanical valves who, therefore, need to restart anticoagulation early.

Mitral paravalvular leaks

Most operators use antegrade access (left atrium-ventricle) through a femoral vein and via transseptal access. To perform this technique, it is essential to use good 3D transesophageal echocardiography imaging support plus a catheter with flexion capabilities to guide the latter over the origin of the leak. In most cases, placing a high-support guidewire inside the left ventricle makes the creation of an arteriovenous loop unnecessary (that would require arterial access). Therefore, in most cases, 1 single venous access is often enough. The devices used are often the same ones used in aortic leaks and the necessary catheters have the same size. We should mention that occasionaly mitral leaks require multiple device implantation. If simultaneous implantation of 2 or more devices is required, it may be necessary to perform as many venous accesses as devices will be eventually implanted. Alternatively, mitral paravalvular leaks can be crossed retrogradely (ventricle-left atrium). This technique requires manipulating catheters inside the left ventricle with the corresponding high risk of arrhythmia. It can be an alternative when antegrade crossing becomes complicated, and is easier in posterior compared to anterior leaks (since the guidewire always moves through the aorta). Obviously, this technique arterial puncture and the creation of an arteriovenous loop at left atrium level.

Coarctation of aorta

The percutaneous treatment of choice of coarctation of aorta is stenting. Therefore, large size arterial access is required (10-Fr-to-14-Fr) often via femoral access. The caliber of the femoral introducer sheath depends on the selection of balloons and stents that will eventually be used. Stents can be covered or not. Covered stents are often used for complex coarctations like those with complete obstructions or critical stenoses with risk of rupture, those associated with aneurysms, pseudoaneurysms, ductus arteriosus or diseased wall (bicuspid Valve, Turner). In elderly patients the use of covered stents can cover dissections or ruptures. Apart from the risk of proximal branch occlusion, the setback of using covered stents is that these need sheaths that should be > 3-Fr compared than the ones needed for the balloon. Overall, the sheaths should be 2-Fr-to-3-Fr larger than the minimum size required by the balloon to give the stent enough space to move freely inside.

Regarding femoral arterial access, we should not forget that the arterial vasculature of patients with coarctation of aorta has a smaller than normal diameter in the lower limbs. Also, an additional radial arterial access can be useful for visualization purposes, as well as the angiography during the procedure. Also, to cross critical coarctations or complete occlusions. In rare cases, carotid access can be necessary to reach the descending aorta (neonates, critical stenoses).15

Regarding closure, since the sheath is often 12-Fr-to-14Fr, vascular closure with the aforementioned specific devices or else delayed manual compression after heparinization has been reversed is often advised.16

Closure of the ductus arteriosus

To perform the closure of ductus arteriosus, the femoral vein and artery are often catheterized. Left and right heart catheterization is advised to register pulmonary and systemic pressures, which is why it is reasonable to use venous access using a 7-Fr introducer sheath. Large sized occlusion devices for ductus arteriosus are also compatible with 7-Fr and often implanted through the venous side, which is why an early 5-Fr arterial access can be planned—often via femoral access—thus, the need for an arteriovenous loop can be anticipated. However, it can also be performed via radial access with a potential reduction of vascular complications. When femoral venous access is not possible (femoral bilateral occlusion or the inferior vena cava) and access underneath the right atrium is preferred (as in the case of the percutaneous closure of ductus arteriosus or interatrial septum defects), the use of other access routes like the transhepatic one have been described.17

Regarding the caliber of vascular accesses, we should take into consideration both the technique selected and the type and size of device used. There are 2 different percutaneous treatment options available regarding persistent ductus arteriosus: coils or occlusion devices. If we’re dealing with a small ductus (< 4 mm) 1 or several controlled-release coils compatible with small sized catheters (4-Fr) and even microcatheters can be used. For larger ductus, occlusion devices are preferred. They are all self-expandable nitinol coils compatible with 5-Fr-to-7-Fr introducer sheaths depending on their size.

Catheterization of ductus arteriosus is performed via antegrade access (from the pulmonary artery) or retrogradely (from the aorta). If so, an arteriovenous loop is required. In both cases, the device introducer sheath is inserted through the antegrade venous side from where it is implanted. Regarding closure, since these are not large caliber accesses—the largest one being via venous access—manual compression is often performed.


Ultrasound-guided venous puncture technique

Transfemoral venous access is the most widely used to perform non-TAVI percutaneous structural heart procedures. Right heart chambers can be accessed via femoral vein. Left heart chambers, however, are accessed through transseptal punctures.

Traditionally, venous puncture has been performed using anatomy-guided references. Experienced operators achieve reasonable rates of success through this method. However, there is a non-negligible chance of complications like inadvertent arterial puncture, venoarterial fistula, pneumothorax (in the internal jugular venous access), nervous lesion or multiple failed catheterization attempts. The risk and the consequences of these complications depend on the type of patients treated. Risk factors like obesity, cachexia, previous radiotherapy or previous surgical scars, among others, can impact the success of catheterization and the appearance of complications.18

The safest technique for venous catheterization is ultrasound guided. To identify the vein that should be punctured and establish its association with the accompanying artery pressure with the ultrasound probe should be exerted in such a way that the vein—not the artery—will often collapse (see sections above).

There are 2 techniques available to perform ultrasound-guided venous punctures: the cross-sectional approach (out-of-plane) and the longitudinal one (in-plane).19 Both have advantages and disadvantages. The former allows us to see, in the same view, the adjacent structures we should avoid during puncture. However, with this approach it is more difficult to see the tip of the puncture needle. Therefore, the angle of the probe should be adjusted to make the views of needle and probe meet. The latter allows us to follow the trajectory of the needle since it first enters the skin until it contacts the target vein. However, the adjacent structures—above all the accompanying artery—cannot be seen in the same view. The target vein can be better seen using the Valsalva maneuver.

Percutaneous closure devices via venous access

Traditionally, venous puncture wound hemostasis has been performed through prolonged manual compression followed by the application of compressive bandage. With the use of larger introducer sheaths to perform structural heart procedures—above all in femoral venous access—safer and more effective methods to achieve hemostasis are under way.

Figure-of-eight subcutaneous suture technique

This technique consists of passing a subcutaneous suture proximally and cross-sectionally to the entry of the venous introducer sheath. Afterwards, the opposite side is crossed, and a subcutaneous suture is performed distally to the sheath entry. Suturing creates a skin and subcutaneous cellular tissue-cinching effect by exerting pressure on the femoral vein. This technique is complemented with mild compressive bandage. A modified technique has been described by performing the subcutaneous suture longitudinally—not cross-sectionally—to the trajectory of the vein looking to minimize the possibility of inadvertent puncture of the vein.20

Vascular closure devices

Angioseal has been used via femoral venous access with up to 8-Fr sheaths with good results.21 The use of percutaneous suture devices like the Proglide has proven safe and effective in the femoral venous access with sheaths of up to 24-Fr.22 Implantation technique is the same as the one used in the artery (see sections above). Depending on the result of the closure, it can be combined with the subcutaneous «figure-of-eight» suture in cases when early hemostasis is not complete. It is often completed with mild compressive bandage.

Particularities of percutaneous mitral valve repair

The most widely used percutaneous coronary intervention on the mitral valve is the so-called «edge-to-edge» repair using the MitraClip (Abbott Vascular, United States) or Pascal devices (Edwards Lifesciences; United States). However, there are direct annuloplasty devices available that replicate a similar repair compared to the surgical one. Also, other transcatheter mitral valve repair options are being developed—some of them completely percutaneous—with good results.

The most widely used vascular access regarding percutaneous coronary interventions on the mitral valve is the femoral vein given its caliber, accessibility, and how easy it is to close after the procedure has been completed. Selecting the left or the right femoral vein depends on the patient’s clinical circumstances (having 2 accesses available, previously operated vascular disease in either one of the 2 accesses, etc.), and the operator’s preference regarding implantation. Therefore, the most widely used access is the right femoral vein that is more comfortable for the operator and uses less radiation.

The possibility of performing implantation via right jugular access has been reported. However, only anecdotal cases have been published due to the difficulties associated with femoral access like the presence of an occluded filter in the inferior vena cava or very sharp angulations of venous iliofemoral axis.23 Technically, implantation is more difficult and has multiple considerations although puncture is basically the same as the routine one.

Ultrasound-guided venous puncture limits its possible complications and should be generalized. In most cases, preclosure devices are implanted before starting the procedure. After inserting a high-support guidewire until the superior vena cava (or inferior if access is jugular) access dissection with forceps is attempted followed by access predilatations with different caliber dilators. Then, the guide catheter is advanced until it reaches the right atrium. Its advance is less complicated compared to the arterial access and with less resistance too. The caliber of the MitraClip guide catheter can be up to 24-Fr—22-Fr with the Pascal device for valve implantation (mitral or aortic in the mitral position)—varies depending on the type of device that should be implanted.

Particularities of tricuspid valve interventional procedures

Percutaneous coronary interventions of the tricuspid valve have evolved over the last decade acting efficiently on leaflet coaptation with suture or ring annuloplasties and eventually with orthotopic or heterotopic percutaneous valve repair.24

The access most widely used is venous access via femoral or jugular vein or both. Depending on the type of procedure used, an additional venous or arterial access or should be attempted—preferably radial—given its lower rate of vascular complications.

Currently, the most widely used device to treat tricuspid regurgitation is the TriClip device (Abbott Vascular) since it was awarded the CE marking back in 2020. With the development of the specific TriClip device—that has a specific wheel to distance itself from the interatrial septum—the right or left venous access does not affect implantation. Therefore, most operators use the right femoral vein as the access route.25

Regarding the implantation of orthotopic or heterotopic valves, access of choice is right femoral access with different calibers depending on the device that should be used (between 14-Fr and 30-Fr).

Particularities of interventional pulmonology procedures

Percutaneous coronary interventions on the pulmonary valve or artery always require a highly variable venous access in its diameter depending on the technique that should be used. Access via femoral vein is the most common one. Therefore, increasing the size of introducer sheaths is not such a big deal as it is the case with arterial accesses.

Percutaneous pulmonary valve implantation requires the use of 16-Fr-to-22-Fr introducer sheaths depending on the model. In many cases, high-support guidewires are required to rectify curvatures in the trajectory of right heart chambers.

Acute treatment of pulmonary thromboembolic disease requires the use of thrombus extraction systems. Since the main determinant of the system that should be used is the size of target thrombus and since the pulmonary artery can accommodate large thrombi, some systems required large caliber accesses. For example, the Penumbra system (Penumbra Inc, United States) can navigate through 8-Fr, Nautilus system (iVascular, Spain) through 10-Fr, and the Flowtriever system (Inari Medical Inc, United States) through 16-Fr-to-24 Fr.

In other cases of more distal thrombectomy or pulmonary angioplasty in chronic thromboembolic disease much smaller introducer sheaths are required (6-Fr-to-7-Fr). Guide catheter extension systems (catheters inside catheters) can be very useful in some cases of difficult access and may require larger introducers sheaths.

Particularities of the left atrial appendage closure

Percutaneous closure of left atrial appendage is often performed via femoral venous access. Some operators perform an additional arterial access to monitor arterial pressure invasively. This arterial access should be performed via radial access to reduce hemorrhagic complications. In some cases, the guidewire is performed with intracardiac ultrasound guidance. In this case, an additional venous femoral access is required.

A key aspect to select the caliber of the venous introducer sheath through which the device should be implanted is the type and size of the introducer sheath. The most widely used devices in our setting are the Amplatzer/Amulet (Abbott Vascular), the Watchman (Boston Scientific, United States), and the Lambre (Lifetech, China).26 Size of introducer sheaths goes from 8-Fr-to-10-Fr (with Lambre) up to 12-Fr-to-14-Fr (with Amulet and Watchman Flx).

Regarding vascular closure, most operators still use manual compression or «figure-of-eight» suture for venous access. However, the aforementioned vascular closure devices can also be used.

Particularities of venous access in other structural heart procedures

There are other structural heart procedures that require venous access, mainly via femoral vein. Some of the most prevalent ones are the closure of patent foramen ovale and interatrial communications. In some cases, these are intracardiac ultrasound-guided procedures, meaning that they require an additional venous femoral access. There are several devices manufactured by different companies to close these entities. However, the most common ones are the Amplatzer PFO occluder, the Amplatzer ASD occluder, and Gore devices, above all, the Gore Cardioform device (WL Gore & Associates, United States). In case of the Amplatzer devices, 8-Fr-to-12-Fr introducer sheaths are required. The Gore system requires short 11-Fr introducer sheaths that are already pre-mounted on a delivery sheath. Overall, the rate of vascular complications is low since these are often young patients who require 1 single femoral venous access only. In case of inferior vena cava occlusion, jugular vein implantation has been reported.27


None whatsoever.


All the authors contributed to the manuscript draft and critical review.


X. Freixa is a proctor for Abbott Medical. R. Romaguera is an associate editor of REC: Interventional Cardiology; the journal’s editorial procedure to ensure impartial handling of the manuscript has been followed. Also, he is a proctor for Boston Scientific and has received conference fees from Medtronic. R. Trillo is a proctor for Medtronic and Boston Scientific. A. Jurado-Román has received conference fees from Boston Scientific.


Vídeo 1. Freixa X. DOI: 10.24875/RECICE.M22000331


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2. Toggweiler S, Leipsic J, Binder RK, et al. Management of vascular access in transcatheter aortic valve replacement: part 2: Vascular complications. JACC Cardiovasc Interv. 2013;6:767-776

3. Leon MB, Smith CR, Mack MJ, et al. Transcatheter or Surgical Aortic-Valve Replacement in Intermediate-Risk Patients. N Engl J Med. 2016;374:1609-1620.

4. Forrest JK, Deeb GM, Yakubov SJ, et al. 2-Year Outcomes After Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients. J Am Coll Cardiol. 2022;79:882-896.

5. van Wiechen MP, Tchetche D, Ooms JF, et al. Suture- or Plug-Based Large-Bore Arteriotomy Closure: A Pilot Randomized Controlled Trial. JACC Cardiovasc Interv. 2021;14:149-157.

6. Junquera L, Urena M, Latib A, et al. Comparison of Transfemoral Versus Transradial Secondary Access in Transcatheter Aortic Valve Replacement. Circ Cardiovasc Interv. 2020;13:e008609.

7. Jimenez-Quevedo P, Nombela-Franco L, Munoz-Garcia E, et al. Early clinical outcomes after transaxillary versus transfemoral TAVI. Data from the Spanish TAVI registry. Rev Esp Cardiol. 2021;75:479-487.

8. Schafer U, Ho Y, Frerker C, et al. Direct percutaneous access technique for transaxillary transcatheter aortic valve implantation: “the Hamburg Sankt Georg approach”. JACC Cardiovasc Interv. 2012;5:477-486.

9. Amat-Santos IJ, Santos-Martinez S, Conradi L, et al. Transaxillary transcatheter ACURATE neo aortic valve implantation - The TRANSAX multicenter study. Catheter Cardiovasc Interv. 2021;98:E291-E298.

10. Hameed I, Oakley CT, Hameed NUF, et al. Alternate accesses for transcatheter aortic valve replacement: A network meta-analysis. J Card Surg. 2021;36:4308-4319.

11. Panagides V, Kalavrouziotis D, Dumont E, et al. Cranial nerve injury during transcarotid transcatheter aortic valve replacement. Int J Cardiol. 2022;353:46-48.

12. Greenbaum AB, Babaliaros VC, Chen MY, et al. Transcaval Access and Closure for Transcatheter Aortic Valve Replacement: A Prospective Investigation. J Am Coll Cardiol. 2017;69:511-521.

13. Giacchi G, Freixa X, Hernández-Enríquez M, et al. Minimally Invasive Transradial Percutaneous Closure of Aortic Paravalvular Leaks: Following the Steps of Percutaneous Coronary Intervention. Can J Cardiol. 2016;32:1575.e17-e19.

14. Estévez-Loureiro R, Benito-González T, Gualis J, et al. Percutaneous paravalvular leak closure after CoreValve transcatheter aortic valve implantation using an arterio-arterial loop. J Thorac Dis. 2017;9:E103-E108.

15. Singh HS, Benson LN, Osten M, Horlick E. Cardiac Catheterization in Adult Congenital Heart Disease. En: Gatzoulis MA, Webb Piers GD, Daubeney EF. Management of Adult Congenital Heart Disease. 3rd edition. Elsevier; 2018. ISBN: 978-0-7020-6929-1.

16. Salinas P, Sánchez-Recalde A, Galeote G, et al. Intervencionismo percutáneo sobre coartación aórtica en el paciente adulto. En: Martín-Moreiras J, Cruz-González I. Manual de Hemodinámica e Intervencionismo Cardiaco. Marbán; 2014. ISBN: 978-84-7101-904-0.

17. Ebeid MR. Transhepatic vascular access for diagnostic and interven- tional procedures: Techniques, outcome and complications. Catheter Cardiovasc Interv. 2007;69:594–606.

18. National Institute for Health and Care Excellence. Guidance on the use of ultrasound locating devices for placing central venous catheters. NICE. 2002. Available online https://www.nice.org.uk/guidance/ta49/resources/guidance-on-the-use-of-ultrasound-locating-devices-for-placing-central-venous-catheters-pdf-2294585518021. Accessed 1 Jun 2022.

19. Privitera D, Mazzone A, Pierotti F, et al. Ultrasound-guided peripheral intravenous catheters insertion in patient with difficult vascular access: Short axis/out-of-plane versus long axis/in-plane, a randomized controlled trial. J Vasc Access. 2021. https://doi.org/10.1177/11297298211006996.

20. Wyss CA, Anliker O, Gämperli O, et al. Closure of Large Percutaneous Femoral Venous Access Using a Modified “Figure-of-Eight” Suture. Innovations (Phila). 2018 Mar/Apr;13(2):147-151

21. Coto HA. Closure of the femoral vein puncture site after transcatheter procedures using Angio-Seal. Catheter Cardiovasc Interv. 2002;55:16-19.

22. Geis NA, Pleger ST, Chorianopoulos E, et al. Feasibility and clinical benefit of a suture-mediated closure device for femoral vein access after percutaneous edge-to-edge mitral valve repair. EuroIntervention. 2015;10:1346-1353.

23. Yap J, Chen S, Smith TWR, at al. Transjugular mitral valve repair with the MitraClip: A step-by-step guide. Catheter Cardiovasc Interv. 2020;96:699-705.

24. Asmarats L, Puri R, Latib A, Navia JL, Rodés-Cabau J. Transcatheter Tricuspid Valve Interventions: Landscape, Challenges, and Future Directions. J Am Coll Cardiol. 2018;71:2935-2956.

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* Corresponding author.

E-mail address: freixa@clinic.cat (X. Freixa).


El estudio de la fisiología coronaria ha pasado de ser una técnica de investigación hace algunos años a convertirse en una herramienta necesaria para el abordaje óptimo de los pacientes con enfermedad coronaria epicárdica y para evaluar la microcirculación. La realización de estas técnicas requiere el uso de una guía de presión para la que hacen falta medios técnicos, tiempo y práctica en su ejecución, y es en parte por ello que su utilización es baja. Existe la necesidad de conocer la evidencia actualizada, las técnicas disponibles y la forma idónea de aplicarlas para ofrecer el mayor beneficio a los pacientes. Esta revisión ofrece un resumen práctico sobre el estado actual de los estudios de fisiología coronaria, con el fin de facilitar el mejor uso posible de esta herramienta diagnóstica esencial.

Palabras clave: Enfermedad coronaria. Fisiología coronaria. Angina microvascular.


The study of coronary physiology has evolved from a research topic to a necessary component for the optimal management of patients with coronary artery disease when assessing both epicardial and microvascular coronary segments. The performance of these techniques requires the use of pressure wires with additional supporting systems, time, and practice, which explains the overall low rate of usage. It is essential to know the updated evidence, the techniques available, and how to perform them properly to offer the greatest possible benefit to our patients. This review provides a practical overview on coronary physiology, and it is ultimately aimed at improving the quality of care.

Keywords: Coronary artery disease. Coronary physiology. Microvascular angina.

Abbreviations FFR: fractional flow reserve. iFR: instantaneous wave-free ratio. IMR: index of microcirculatory resistance. Pd/Pa: distal to aortic coronary pressure. QFR: quantitative flow ratio.


For decades angiography has been used as the reference procedure to diagnose coronary artery disease. However, this technique spares the physiological repercussion of epicardial coronary stenoses. Thus, by the end of the 20th century the functional characterization of coronary circulation thanks to the development of various tools both invasive (specific intracoronary guidewires) and non-invasive (angiography-derived indices) started gaining interest. The result was a change of paradigm in the diagnosis and management of coronary artery disease from an angiography to an ischemia-based strategy.1 This has become possible thanks to the abundant scientific evidence available supporting the use of physiological indices leading the ischemia-based strategy to the highest level of recommendation in the latest European guidelines on the management of myocardial revascularization.2 However, the recent publication of some clinical trials has put into question the impact of coronary physiology in certain clinical settings like multivessel disease and ST-segment elevation acute coronary syndrome (STEACS).3,4 On the other hand, these techniques take time, the use of coronary invasive instruments and, at times, the administration of vasodilators that are not always well tolerated by the patients. Also, a certain clinical experience is required. For all this, the adoption of physiology techniques to guide revascularization is still far from overall implantation.5

Over the following paragraphs we’ll be taking a practical approach on the physiological assessment of coronary stenosis and microcirculation using invasive and angiography-derived indices. Details of the physiological concepts behind every index will be left out or specific texts will be pointed out for that matter.

Physiological assessment of coronary stenoses

Invasive indices

Coronary fractional flow reserve (FFR) index is the ratio of maximum myocardial blood flow in the presence of a single stenosis with respect to the anticipated normal flow for the lack of stenosis; it is expressed as a fraction of its normal anticipated value. It is obtained by measuring intracoronary pressure with guidewires specifically designed for that matter. Determining FFR requires the vasodilation of microcirculation by using drugs, adenosine mainly—IV regadenoson and intracoronary nitroprusside have been used with similar results.6 Also, the measurement of minimal distal to aortic coronary pressure ratio (Pd/Pa) after the injection of intracoronary contrast (cFFR).7 Therefore, it is a hyperemic coronary physiological index. It is based on the fact that, in a situation of maximum hyperemia, a linear correlation between relative flow and relative intracoronary pressure is achieved since coronary resistance is both stable and minimum.8 Its result is independent of microcirculation, heart rate, arterial blood pressure, and other hemodynamic variables. The European guidelines on the management of chronic coronary syndrome give FFR an indication I, Level of Evidence A, for risk stratification in symptomatic patients who are unresponsive to medical therapy and asymptomatic patients in whom non-invasive tests show a high risk of events, and an indication type IIa when the results of non-invasive tests are inconclusive.1

A summary of the FAME trials (Fractional flow reserve vs angiography for multivessel evaluation) is shown on table 1.4,9-11 These results reinforce the need for studying the physiology field and individualizing the management of our patients inside the heart team.

Table 1. Summary of results from the FAME trial

Study Year N Population Comparison Follow-up Primary endpoint Death Myocardial infarction New revascularization Other results
FAME9 2009 CCS: 677
UA: 328
Stenosis ≥ 50% in 2 or more vessels, eligible for PCI PCI with angiography-guided vs FFR-guided DES (≤ 0.80) 1 year Death, AMI, new revascularization: 13.2% vs 18.3%; HR, 0.72; 95%CI, 0.54-0.96 1.8% vs 3.0%; HR, 0.58; 95%CI, 0.26-1.32 5.7% vs 8.7%; HR, 0.66; 95%CI, 0.42-1.04 6.5% vs 9.5%; HR, 0.68; 95%CI, 0.45-1.05 No differences in the events reported separately
No differences in the rate of angina reported
Less use of resources with FFR
FAME 210 2012 CCS: 888 ≥ 1 stenosis in 1 epicardial coronary artery with FFR ≤ 0.80 PCI with second-generation stents and OMT vs OMT 7 months (mean) Death, AMI, emergency revascularization: 4.3% vs 12.7%; HR, 0.32; 95%CI, 0.19-0.53 0.2% vs 0.7%; HR, 0.33; 95%CI, 0.03-3.17 3.4% vs 3.2%; HR, 1.05; 95%CI, 0.51-2.19 Emergency: 1.6% vs 11.1%; HR, 0.13; 95%CI, 0.06-0.30
Non-emergency: 1.6% vs 8.6%; HR, 0.17; 95%CI, 0.08-0.39
No significant differences in the composite of death and AMI or cardiac death
FAME 2 – 5 years11 2018 CCS: 888 ≥ 1 stenosis in 1 epicardial coronary artery with FFR ≤0.80 PCI with second-generation stents and OMT vs OMT 5 years Death, AMI, emergency revascularization: 13.9% vs 27.0%; HR, 0.46; 95%CI, 0.34-0.63 5.1% vs 5.2%; HR, 0.98; 95%CI, 0.55-1.75 8.1% vs 12.0%; HR, 0.66; 95%CI, 0.43-1.00 Emergency: 6.3% vs 21.1%; HR, 0.25; 95%CI, 0.18-0.41
Non-emergency: 7.6% vs 35.1%; HR, 0.18; 95%CI, 0.12-0.26
No significant differences regarding death and AMI
The percentage of patients with angina is lower within the first 3 years being this difference non-significant at 5 years
FAME 34 2022 CCS: 1500 3-vessel disease Non-inferiority design: FFR-guided PCI (≤ 0.80) vs coronary revascularization surgery 1 year Death, AMI, stroke. new revascularization: 10.6% vs 6.9%; HR, 1.5; 95%CI, 1.1-2.2; P = .35 for non-inferiority 1.6% vs 0.9%; HR, 1.7; 95%CI 0.7-4.3 5.2% vs 3.5%; HR, 1.5; 95%CI, 0.9-2.5 5.9% vs 3.9%; HR, 1.5; 95%CI, 0.9-2.3 No significant differences in the composite endpoint of death, infarction, stroke
Less major bleeding, kidney damage, AF, and rehospitalization at 30 days with PCI

95%CI, 95% confidence interval; AF, atrial fibrillation; AMI, acute myocardial infarction; CCS, chronic coronary syndrome; DES, drug-eluting stent; FAME, fractional flow reserve vs angiography for multivessel evaluation; FFR, fractional flow reserve; HR, hazard ratio; OMT, optimal medical therapy; PCI, percutaneous coronary intervention; UA, unstable angina.

Hyperemia, especially the one obtained with IV adenosine—needed to obtain FFR—takes time, is expensive, changes systemic hemodynamics, and can cause unpleasant side effects (conduction disorders, chest pain, nausea, dyspnea, dizziness, flashing, and headache). Therefore, after its arrival, resting indices—that do not require hyperemic drugs—soon gained popularity. Overall, these indices are phasic—unlike FFR that is rather based on mean pressures—and are measured in the middle or late portion of the diastolic period when there is a greater transstenotic flow naturally.6 Although the first description of a resting index was given by Grüntzig in his early publication of coronary angioplasty,12 its clinical use did not become popular until the appearance of the instantaneous wave-free ratio (iFR, Philips, The Netherlands). Several studies were conducted to compare the diagnostic concordance of iFR and FFR, as well as iFR, FFR, and other reference parameters of ischemia.13,14 Two multicenter randomized clinical trials—the DEFINE-FLAIR (Functional lesion assessment of intermediate stenosis to guide revascularization) and the iFR-SWEDEHEART (Evaluation of iFR vs FFR in stable angina or acute coronary syndrome)—randomized 4529 patients to receive FFR or iFR-guided percutaneous revascularization in both patients with ACS and chronic coronary syndrome.15,16 Both studies demonstrated the non-inferiority of the iFR compared to the FFR with low rates of events defined as all-cause mortality, acute myocardial infarction or unplanned revascularization at 1 year: iFR, 4.12% vs FFR, 4.05%; hazard ratio (HR), 1.13; 95% confidence interval (95%CI), 0.72-1.79; P = .60). Also, in the iFR groups, the number of functionally significant stenoses and rates of revascularization were lower, procedural time was shorter, and there were fewer patients with adverse symptoms associated with the administration of adenosine.15,16 Over the last few years, several resting indices have been developed based on the concept previously described: DFR (diastolic hyperemia-free ratio, Boston Scientific, United States),17 and the resting diastolic pressure ratio (dPR) (ACIST, United States).18,19 Except for the resting full-cycle ratio (RFR) (Abbott, United States),18 that is a non-hyperemic index to assess pressure along the entire cardiac cycle (table 2), all resting indices are highly reproducible, and identical to iFR both numerically and in their concordance with FFR.19 The prognostic capability of the Pd/Pa ratio is less robust compared to the FFR21 since its correlation with FFR in non-culprit lesions of patients who had an ACS is 80%;22 after the arrival of non-hyperemic indices, its clinical significance is scarce.

Table 2. Indices used to study epicardial coronary stenoses

Vasodilation Period of cycle Cut-off value Scientific evidence
iFR Non-hyperemic Diastolic ≤ 0.89 RCTs: DEFINE-FLAIR, iFR-SWEDEHEART
Observational: SYNTAX II
DFR Non-hyperemic Diastolic ≤ 0.89 Observational: Johnson et al.14
dPR Non-hyperemic Diastolic ≤ 0.89 Observational: Lee et al.,15 Van’t Veer et al.16
RFR Non-hyperemic The full cycle ≤ 0.89 Observational: Lee et al.15
Pd/Pa Non-hyperemic The full cycle 0.91-0.93 Observational: Kobayashi et al.,20 Lee et al.15

DFR, diastolic hyperemia-free ratio; dPR, resting diastolic pressure ratio; FFR, fractional flow reserve; iFR, instantaneous wave-free ratio; Pd/Pa, distal to aortic coronary pressure ratio; RCT, randomized clinical trials; RFR, resting full-cycle ratio.

Supplementary data provides a detailed description on the practical management of invasive physiological indices.


Figure 1 shows the steps needed to measure resting indices and FFR. Supplementary data gives a step-by-step detailed description. Figure 2 shows the utility of pressure guidewires for the diagnosis and location of significant stenoses.

Figure 1. Steps to use intracoronary pressure guidewire to measure resting indices and fractional flow reserve. Ao, aorta, FFR, fractional flow reserve; IC, intracoronary; IV, intravenous. * Catheter purged with saline solution and no guidewire introducer sheath.

Figure 2. A: angiography of right coronary artery showing diffuse damage with more severe lesions at distal level (asterisks). B: pullback resting full-cycle ratio (RFR) measurement showing 2 focal jumps corresponding to the asterisks shown on A. C: final angiographic outcomes after implantation of 2 drug-eluting stents. D: final RFR with optimal result of 0.98.

Problems, causes, solutions, and specific settings

Table 3 shows some of the main problems that can be found when performing pressure guidewire studies, their causes, and possible solutions. Supplementary data provides a detailed description on how to deal with these problems, and a description on the use of pressure guidewire in different clinical settings (diffuse coronary artery disease, ostial lesions, aortic stenosis, ACS, post-angioplasty assessments).

Table 3. Pressure guidewire: main problems, causes, and possible solutions

Problem Cause Recommendations
Aortic pressure damping Catheter/vessel mismatchOstial lesion Use a guide catheter of a smaller diameterDisengage the ostium to take better measurements
Falsely reduced aortic pressure Loose connections of the guide catheterAvoid removing the guidewire introducer sheathPresence of contrast in the catheter Double check all connections before taking any measurementsAlways remove the guidewire introducer sheathPurge the guide catheter with a saline solution
Loss of drift Need for multiple connections/disconnectionsProlonged procedure Repeat equalization and measurementEqualizing should precede any measurements after the PCIUse fiber optic guidewires if prolonged procedure is anticipated
Spasm, pseudostenosis Presence and manipulation of intracoronary guidewireExcessive tortuosity Always administer IC nitrates before the procedureAdditional dose of IC nitrates if suspected pseudostenosisConsider alternative methods in case of excessive tortuosity
Scarce response to adenosine Use of caffeine, theobromine (chocolate), theophyllineInappropriate intracoronary administration Talk to the patients and tell them that the use of coffee/chocolate/theophylline is ill-advised 24 hours before the procedureIC administration or IV perfusion of adenosine at 210 μg/kg/minGuarantee proper catheterization for the administration of IC adenosineNeve use IC adenosine with a catheter with lateral holes
Excessive measurement variability Patient movingArrythmias (AF) Make sure that the patient is comfortableRepeat measurement in the presence of cough or sudden movesSelect measurement sites manually on the console

AF, atrial fibrillation; IC, intracoronary; IV, intravenous; PCI, percutaneous coronary intervention.

Angiography-derived indices

The physiological study of epicardial stenoses is limited in the routine clinical practice due to the need for pressure guidewires and, in some cases, hyperemic agents that take up higher costs and possible side effects.23 Therefore, new angiography-derived indices like QFR, angio-FFR, CAAS-vFFR, and vFFR have been produced. These are based on 3D reconstructions of coronary tree through the angiography and then computational flow dynamics software or mathematical simplifications of it as a surrogate of coronary flow.

QFR (quantitative flow ratio; Qangio XA 3D, Medis Medical Imaging Systems, The Netherlands) uses a 3D reconstruction of the angiography. Afterwards, assuming a constant pressure and velocity of flow along a normal epicardial vessel, a proxy of the FFR value is estimated using different models: the fixed model (fQFR) uses information from a database from which FFR values and flow velocities have been previously obtained; the contrast-QFR model (cQFR) takes into account the flow velocity of the contrast injected into the epicardial artery by counting frames; and the QFR-adenosine model (aQFR) that studies it after inducing hyperemia through the administration of adenosine. The 3 models were tested against FFR, and the best diagnostic accuracy was obtained with the QFR-adenosine (87%) and cQFR (86%) models.24 Several studies conducted later have demonstrated the utility and high accuracy of this model for the functional diagnosis of epicardial stenosis,25,26 and how safe the revascularization decision is based on such model.27,28 The FAVOR III China trial of 3825 patients confirmed fewer major adverse events (HR, 0.65; 95%CI, 0.51-0.83; P = .0004) in patients with delayed revascularization based on QFRs ≤ 0.80 triggered by fewer myocardial infarctions and ischemia-guided revascularizations compared to angiography-guided revascularizations.28

Another index is the CAAS-VFFR (Cardiovascular angiographic analysis system for vessel FFR, CAAS-vFFR, Pie Medical, The Netherlands). It is based on a 3D reconstruction of the angiography acquired followed by an estimate of the pressure gradient through a lesion. Its validation study included patients with stable disease and non-ST-segment elevation acute coronary syndrome and showed a 93% accuracy for the diagnosis of lesions with FFR ≤ 0,80, and a 95% inter-observer correlation.29

Angio-FFR index (Cathworks, Israel) is also widely used. Unlike the former indices presented above, it uses, at least, 3 different angiographic views to sketch a 3D functional angiography mapping. Fearon et al.30 studied it in a large population and confirmed sensitivity, specificity, and diagnostic accuracy values of 94%, 91%, and 92%, respectively for FFR ≤ 0.80 with 96% high inter-observer consistency.

Other indices like the vFFR (virtual fractional flow reserve, VirtuHeart Medical Physics Group, United Kingdom) demonstrated, in its validation study, high diagnostic accuracy, sensitivity, and specificity of 97%, 86%, and 100%, respectively.31 This index, however, is still in the pipeline.

Recently, a meta-analysis conducted by Collet et al.32 demonstrated that angiography-based FFR measurements have an overall sensitivity and specificity of 89% and 90% compared to invasive FFR. However, there can be a relatively large gray area (0.75-0.86) where the invasive determination of FFR could be indicated.33 Assuming this gray area, the diagnostic accuracy of these methods could be > 95% like the FAVOR II China trial proved,25 preventing the need for an invasive study in 64% of the lesions.34

Despite the promising results obtained, these analyses have certain limitations. One of the main ones is to obtain proper angiographies for analysis without structure panning or overlapping.35 Another one is anatomy since the contouring of ostial or bifurcation lesion borders is more difficult to achieve meaning that its study may be biased. In a recent analysis on the population of the SYNTAX II trial, QFR assessment vs hybrid iFR/FFR assessment demonstrated a diagnostic accuracy of QFR close to 74% with a 8.3% rate of false positives and a 17.9% rate of false negatives being the main reasons for this mismatch the lesions found in marginal branches, small vessels or bifurcation regions.35 Also, the state of microcirculation is especially interesting since these techniques assume maximum vasodilation to estimate pressure from the flow obtained. However, the degree of response to hyperemia—whether due to contrast or pharmacological agents—is variable based on each patient’s state of microcirculation and, therefore, subject to error. Mejía-Rentería et al.36 reported on how the state of microcirculation impacts this type of non-invasive assessments of coronary flow reserve (CFR), and saw that the greatest source of mismatch came from an impaired microvascular function measured as an impaired value of the index of microcirculatory resistance (IMR) or situation of acute myocardial infarction. One could think that image processing time and its analysis can be longer compared to the physiological study using pressure guidewires. However, if trained, it has been confirmed that the study can be conducted faster compared to the traditional determination of FFR.37,38 Finally, a pending limitation that needs solving is observer-dependent variability (0.01 ± 0.08 match for repeat measurements), the quality of angiography, and the degree of FFR-based stenosis.39

Supplementary data provides a detailed description on the practical management of QFR, angio-FFR, and vFFR.

Physiological assessment of coronary microcirculation

Invasive indices

Although coronary artery disease is often associated with damage to epicardial arteries, up to 25% of the patients with typical angina do not show significant epicardial stenoses.1 Microvascular dysfunction is a contributing factor of angina and individualized treatment has proven to improve the patients’ quality of life,40 which is why a proper intracoronary diagnosis of microvascular disease in symptomatic patients without stenosis or with moderate coronary stenoses has a recommendation IIa in the European guidelines on the management of chronic coronary syndrome.1

Arterioles, the main component of coronary vascular resistance, plays a very dynamic role in coronary blood flow and are regulated by multiple metabolic, myogenic, endothelial, neural, and hormonal mechanisms.41,42 Impaired microcirculation can occur through any of these pathways and bring about unfavorable prognosis similar to that of obstructive epicardial disease.43 The size of these vessels complicates their angiographic assessment, and the use of other methods is essential. CFR measures the ratio of coronary flow in hyperemia compared to resting flow with normal values between 3 and 4 indicative that coronary flow increases by a factor of 3 or 4 with maximum hyperemia. CFR results represent the capacity to increase flow both of epicardial arteries and microvasculature. Reduced CFR is associated with a significant increase of mortality (HR, 3.78; 95%CI, 2.39-5.97), and major adverse cardiovascular events (HR, 3.42; 95%CI, 2.92-3.99) in multiple diseases including patients with ACS, microvascular dysfunction, heart transplant, and diabetes mellitus.44

Microcirculatory resistance can be measured through thermodilution or intravascular Doppler ultrasound in baseline conditions or in hyperemia.45 The IMR—reference index to study microcirculation—is based on measuring distal pressure and coronary flow through thermodilution as assessed by the inverse of the arrival (transit) time of a room temperature saline solution bolus to the artery distal segment during maximum hyperemia. High IMR > 25 is associated with poor cardiovascular prognosis; the combination of low CRF and high IMR is associated with worse prognosis.46,47 Recently, a new method based on thermodilution and a continuous flow of saline solution (RayFlow catheter, Hexacath, France) to estimate absolute coronary flow in hyperemic conditions and absolute microvascular resistance48,49 has been described. Its advantage is that it does not depend on baseline values, which lowers the significance of hemodynamic changes. It does not depend on the operator either. Its clinical utility still needs to be proven given the limitation interpreting absolute values.

The Doppler guidewire estimates the CRF by dividing flow velocity in hyperemia by the baseline flow velocity. Cut-off values of ≤ 2.5 are consistent with a diagnosis of microvascular dysfunction in healthy epicardial arteries.50 The prognostic value of CRF measured invasively through Doppler in patients with angina is independent from the findings of non-invasive modalities with a 5-year HR of 2.97 (95%CI, 1.39-6.34) for major adverse cardiovascular events.51 Hyperemic microvascular resistance (HMR) can also be estimated by dividing intracoronary pressure by hyperemic flow velocity considering that HMR > 1.9 mmHg·cm1·s1 is diagnostic of microcirculatory dysfunction.50 However, it has been reported that HMR ≥ 2.5 mmHg·cm1·s1 has better sensitivity and specificity for the diagnosis of microvascular dysfunction.52

Practical approach


Supplementary data provides a detailed description on the practical management of thermodilution both through boluses (figure 3) and continuous perfusion (figure 4), as well as physiological study using Doppler guidewires (figure 5).

Figure 3. Steps for the study of microcirculation with bolus thermodilution. Ao, aorta; CFR, coronary flow reserve; FFR, fractional flow reserve; IC, intracoronary; IMR, index of microcirculatory resistance; IV, intravenous. * Catheter purged with saline solution and no guidewire introducer sheath.

Figure 4. Steps for the study of microcirculation with continuous thermodilution. Ao, aorta, IC, intracoronary; IV, intravenous. a Catheter purged with saline solution and no guidewire introducer sheath. b Do not switch the transmitter of during the entire procedure.

Figure 5. Steps for the study of microcirculation with intracoronary Doppler guidewire. Ao, aorta; CFR, coronary flow reserve; HMR, hyperemic microvascular resistance; IC, intracoronary; IV, intravenous; Pd, distal coronary pressure. * Catheter purged with saline solution and no guidewire introducer sheath.

Angiography-derived indices

Although assessing the state of microcirculation using the IMR has largely proven its clinical benefit,50,53 its study in the routine clinical practice is limited since pressure guidewires and hyperemic agents are needed. Therefore, recently, different alternatives have been developed to estimate the angiography-derived index of microvascular resistance (IMRangio) using computational fluid dynamics. Several formulae can be used.

The first description was given by De Maria et al.,54 who saw the good diagnostic capabilities (92.4%) of IMRangio vs invasive IMR using a different QFR-adenosine formula in patients with myocardial infarction, and a high correlation between a high value on the IMRangio and the presence of microvascular obstruction as seen on the magnetic resonance imaging.

IMRangio has been studied in both stable patients and patients with ACS55 obtaining a good correlation between IMR and IMRangio and a high diagnostic accuracy of the latter when used with adenosine in patients with ACS and stable patients. However, it was seen that the correlation between IMR and cQFR-derived IMRAngio (NH-IMRangio) did not hold up in non-culprit arteries of the acute event or in cases of greater clinical stability only showing a good correlation in the infarction culprit arteries. Authors think that a possible explanation to this phenomenon would be the greatly impaired vasodilator capability of patients with ST-segment elevation acute myocardial infarction. Therefore, they proposed a hybrid algorithm by means of which it would only be necessary to use adenosine in cases with NH-IMRangio levels > 30 U and < 90 U, which would stop the use of adenosine in 38% of the cases. Also, in cases of ST-segment elevation acute myocardial infarction—where maybe the use of hyperemia may be more limited due to the clinical situation—this group showed that NH-IMRangio levels > 43 could detect IMR values > 40 very precisely and be predictor of long-term events56 without having to use adenosine.

Tebaldi et al.57 use a formula based on the cQFR value (NH-IMRangio) to assess the state of microcirculation in patients with stable angina finding a high correlation between IMRangio > 44.2 and invasive IMR > 25.

Parallel to this, another group used a different formula including the cQFR value58 to assess microvascular function in patients with chronic and acute coronary syndrome that confirmed a good overall diagnostic accuracy. Also, this group proved it could have an added value to reduce the rate of false positives of QFR since an impaired microvascular function can affect the accuracy of the QFR study.36 Recently, a meta-analysis of aggregate data demonstrated the good diagnostic performance of IMRangio compared to invasive IMR, with sensitivity, specificity, accuracy, positive predictive, and negative predictive values of 82%, 83%, 83%, 76%, and 85%.59

FlashAngio (Rainmed, China) is yet another software to determine non-invasive IMR,60,61 with similar diagnostic results. Added to its diagnostic value, Choi et al.61 proved the prognostic value of such index, since high IMRangio levels (< 40 U) were associated with cardiac death and rehospitalization due to long-term cardiovascular problems.

Supplementary data provides a detailed description on the practical management of IMRangio.


The study of coronary physiology is a tremendous breakthrough for the management of patients with coronary artery disease. Being able to fine tune the functional severity of epicardial lesions and how microcirculation impacts the symptomatology of patients allows us to personalize treatment to reduce symptoms and, in many cases, improve prognosis. Great advances have been made in this field achieving further physiological knowledge and greater diagnostic accuracy both with invasive and non-invasive tests. Although extensive, knowledge in this field still shows gaps that will still be solved with new studies. All this development requires specific and updated training so we can take advantage of knowledge and technology for the benefit of our patients.


None reported.


J.P. Vilchez-Tschischke, J. Sanz Sánchez, and E. Fernández Peregrina contributed to the design, drafting, and review process of the article, J.L. Díez Gil, M. Echevarría Pinto, and H.M. Garcia-Garcia contributed to both the drafting of the manuscript and the critical review of its intellectual content.


J. Sanz Sánchez received conference fees from Cordis, and Terumo. H.M. Garcia-Garcia received conference fees from Biotronik, Abbot, Boston Scientific, Neovasc, Medtronic, Shockwave, Philips, and Corflow. The remaining authors declared no conflicts of interest whatsoever.


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* Corresponding authors.

E-mail addresses: drmauroechavarria@gmail.com (M. Echevarria Pinto) and hect2701@gmail.com (H.M. Garcia-Garcia).



Calcified coronary artery disease poses a number of challenges to the interventional cardiologist when performing percutaneous coronary interventions, and patients with calcified coronary artery disease continue to have poorer outcomes at both the short and the long-term follow up. Stent underexpansion is the most feared outcome when performing percutaneous coronary interventions in these patients and is a strong predictor of stent failure. Therefore, intracoronary imaging to guide calcium modification is an important step in the treatment of this disease. The following review outlines a stepwise approach using intracoronary imaging in the assessment of coronary calcification, and in the selection of the appropriate calcium modification tool. Additionally, we describe current calcium modification techniques available, the evidence behind their use, their mechanism of action, and the typical results seen on intracoronary imaging.

Keywords: Coronary calcium. Calcium modification. Atherectomy. Lithotripsy. Optical coherence tomography. Intravascular ultrasound.


Las intervenciones coronarias percutáneas en enfermedad arterial coronaria calcificada representan un desafío para el cardiólogo intervencionista. Además, los pacientes con enfermedad arterial coronaria calcificada tienden a tener peores resultados en el seguimiento a corto y largo plazo. La infraexpansión del stent es el resultado más temido cuando se realiza una intervención coronaria percutánea en estos pacientes y es un gran predictor de falla del stent. Por lo tanto, la modificación del calcio guiada por imágenes intracoronarias, es un paso importante en el tratamiento de esta enfermedad. La siguiente revisión describe el uso «paso a paso» de imágenes intracoronarias en la evaluación de la calcificación coronaria y en la selección de una técnica de modificación de calcio adecuada. Además, se describen las técnicas actuales de modificación de calcio disponibles, la evidencia para su uso, su mecanismo de acción y los resultados típicos que se observan en las imágenes intracoronarias.

Palabras clave: Calcificación coronaria. Modificación de placa calcificada. Aterectomía. Litoplastia. Tomografía coherencia óptica. Ecografía intravascular.

Abbreviations CAD: coronary artery disease. IVI: intravascular imaging. IVL: intravascular lithotripsy. IVUS: intravascular ultrasound. OA: orbital atherectomy. OCT: optical coherence tomography. PCI: percutaneous coronary intervention. RA: rotational atherectomy.


Calcified coronary stenosis is a relatively common finding present in up to 30% of lesions planned for percutaneous coronary intervention (PCI).1 Calcified atherosclerosis presents a number of difficulties when performing PCI especially stent underexpansion, a strong predictor of stent failure (thrombosis and restenosis).2-4 It comes as no surprise, then, that worse clinical outcomes have been found following PCI in moderate-to-severe calcified disease compared to atherosclerotic plaques without calcium.1 A number of plaque modification techniques are available although there is a paucity of head-to-head comparisons among the techniques making device selection difficult. Understanding calcium morphology can contribute to proper device or technique selection, and is best guided by intravascular imaging (IVI). In this review, we outline the assessment of coronary calcium using IVI, propose a simplified calcium modification algorithm we use at our center, and examine the mechanism of action and evidence behind the use of each of these techniques.

Pathophysiology and prognostic implications of coronary calcium

The pathophysiology of atherosclerosis is well documented and starts with injury to the vessel and accumulation of low density lipoprotein which undergoes oxidative changes that result in the release of proinflammatory cytokines. These attract monocytes that migrate towards the intima layer, mature into macrophages, and eventually form foam cells.5 Further recruitment of smooth muscle cells from the media layer produce extracellular matrix that leads to intimal thickening and plaque progression. In time, and in the presence of risk factors including age, male sex, Caucasian race, hypertension, hyperlipidemia, diabetes, and chronic kidney disease, calcification of atherosclerotic plaques can occur and its pathogenesis has much in common with bone formation.1,5-8 Transformation of vascular smooth muscle cells into an osteoblastic phenotype is thought to be the initiation factor prompted by exposure to bone morphogenetic protein-2 (BMP 2) produced by endothelial cells when exposed to stressors like hypoxia, high pressure, turbulent flow, and inflammation.9 The result is the loss of expression of vascular smooth muscle specific markers, and the expression of genes typically found in bone generating cells.10 Other pathways also play a role including apoptosis of vascular smooth muscle cells, and formation of calcifying matrix vesicles by macrophages.6 The early result is the deposition of microcalcifications that eventually coalesce into larger calcium deposits that can be seen as “spotty calcification” on IVI. Further progression ultimately results in calcium sheets or plates which can extend across multiple quadrants of the vessel causing vessel stiffening and altering compliance.11 Nodular calcification, an important morphological subtype which protrudes into the vessel lumen, forms when there is rupture of the calcium sheets.6 Prognostically, the presence of calcified atherosclerosis is associated with poorer cardiovascular outcomes.12,13 Initial spotty calcification represents an unstable period in the evolution of calcified coronary artery disease (CAD), and these lesions are more commonly associated with plaque rupture and acute coronary syndrome.6,14 Conversely, lesions with a higher percentage calcified plaque volume as seen on computed tomography coronary angiography are more stable and present less frequently with acute cardiovascular events, yet more commonly with chronic coronary syndromes and multivessel disease.6,15

Percutaneous coronary intervention in calcified atherosclerosis

Calcific stenoses are found in up to 30% of all patients presenting for PCI.1 The subsequent reduction of coronary artery compliance presents a number of procedural difficulties. Inadequate lesion dilation can potentially result in stent underexpansion,16 one of the most important predictors of stent failure.2-4 Other difficulties include a higher risk of dissection and perforation, difficulty passing equipment distally, damage to the stent polymer, altered drug elution kinetics from stents, and potentially stent deformation or loss.1,17,18 Furthermore, patients with coronary artery calcification are less likely to undergo complete revascularization and more frequently experience adverse outcomes following PCI. In a pooled analysis of the HORIZONS-AMI and ACUITY studies, the presence of moderate or severe calcification (as assessed angiographically) was associated with poorer outcomes at 1 year for all endpoints including death, cardiac death, myocardial infarction, and overall major adverse cardiovascular events.1 As a matter of fact, at 1 year, the risk of stent thrombosis increased by 62% and that of ischaemic target lesion revascularization (TLR) increased by 44% in calcified compared to non-calcified lesions. These findings have been replicated across numerous other studies at both short and long-term follow-up.1,7,19-21 In a recent analysis of the SYNTAXES trial, heavily calcified lesions were associated with a higher all-cause mortality rate after 10 years regardless of the type of revascularization used (hazard ratio, 1.79; 95% confidence interval, 1.49-2.16; P < .001).21 Optimizing the results of PCI is, therefore, of paramount importance with plaque preparation with calcium modification is an important step in this process.

Imaging for calcium detection

Detecting the presence of coronary calcium prior to PCI is important for procedural planning and a number of imaging techniques may be used as shown on table 1.14,15,22-28

Table 1. Summary of available imaging techniques for the detection of coronary calcium

Imaging modality Quantification Sensitivity Specificity Advantages Disadvantages

Computed tomography14,15,22,23

• Calcium scoring on non-contrast images

• Percentage calcified plaque



• Non-invasive

• Calcium scoring provides prognostic information

• Highlights the presence of calcium prior to undertaking an invasive procedure

• Provides some information on the plaque morphology and composition (specific software available)

• Percentage calcified plaque is a predictor of future events

• Blooming artifact can overestimate the degree of calcification

• Circumferential arc difficult to assess

• Radiation exposure

• Contrast use

• Does not provide intraprocedural guidance

Coronary angiography23,24,25

• Mild: not visible

• Moderate: radiopacities seen only with cardiac motion

• Severe: radiopacities seen without cardiac motion, before contrast injection affecting both sides of the arterial wall (tram-track appearance)


+++ in the presence of severe calcification


• Assessment of anatomical complexity, vessel tortuosity, side branch angulation

• Invasive

• No information on calcium morphology (thickness, circumferential arc)


• Calcium thickness

• Calcium circumferential arc

• Calcium length



• High resolution, 10 µm to 20 µm

• Detailed calcium morphological assessment





Presence of calcium nodules

• Procedural guidance

Landing zones

Vessel dimensions

Lesion length

Stent length

Guide stent optimization

Assess stent expansion

Identify complications (dissection, under-expansion, malapposition, stent distortion)

• Co-registration with angiography available

• Invasive

• Requires a blood-free environment for image acquisition

• Contrast required for blood clearance

• Limited assessment of ostial lesions

• Difficult to advance the catheter distally in tortuous vessels


• Calcium arc

• Calcium length



• Moderate-high resolution 100 µm to 150 µm (high-resolution IVUS 20 µm to 30 µm)

• High penetration depth into non-calcific vessel wall ~10 mm

• No specific imaging requirements

• Can assess ostial lesions

• Morphological assessment of calcium



Presence of calcium nodules

• Procedural guidance

Landing zones

Vessel dimensions

Lesion length

Stent length

Guide stent optimization

Assess stent expansion

Identify complications (dissection, underexpansion, malapposition, stent distortion)

• Co-registration with angiography available

• Invasive

• Acoustic shadowing in severe calcification

• Difficult to assess calcium thickness

Use of surrogate markers of thickness (reverberations)

IVUS, intravascular ultrasound; OCT, optical computed tomography.

Non-invasive imaging for coronary calcification

Coronary computed tomography angiography is highly sensitive and specific for the detection of calcium and is a non-invasive technique. Coronary computed tomography angiography can determine plaque morphology and percentage of calcified plaque volume, which has prognostic significance.15 Its utility in procedural planning is increasingly seen in the planning of chronic total coronary occlusions, but it is less useful in the specifics of guiding intraprocedural strategy.

Invasive imaging for coronary calcification

Invasive coronary angiography has long been known to have low sensitivity but high specificity for the detection of coronary calcium. Compared to intravascular ultrasound (IVUS), its overall sensitivity is ~48%, but it increase up to > 85% in the presence of severe (4 quadrant) calcification.24,25 Nonetheless, an arc > 100° as seen on the IVI is required before calcium can be reliably detected on angiography, thus highlighting the potential for calcium to go undetected when the PCI is guided by angiography alone.25 Calcification on angiography is typically classified as none/mild, moderate or severe (table 1). Although angiography provides valuable information to guide the procedure such as vessel tortuosity, angulation of bifurcations, etc, its limitations are well documented, and studies have consistently shown poorer outcomes when PCI is guided by angiography compared to IVI.29-31

IVI overcomes much of the shortfalls of other imaging modalities. Both optical coherence tomography (OCT) and IVUS are more sensitive for the detection of calcium compared to coronary angiography.25 Furthermore, both imaging modalities provide additional information to guide and optimize the procedure (table 1).27 Co-registration with angiography is available for both modalities, and can reduce the learning curve significantly.32 Although the advantages of IVI over angiography have been shown in a number of studies, no randomized studies have specifically examined its potential benefits regarding calcified CAD. Nonetheless, given the complexity of these lesions, performing IVI-guided PCIs seems reasonable.

Intravascular ultrasound

IVUS has both high sensitivity and specificity (86.7% and 93.3%, respectively compared to histological samples) for the detection of dense calcification, although it is less sensitive for the detection of microcalcifications,33 and in the presence of overlying fibrotic plaque.34 Calcium reflects ultrasound resulting in a bright hyperechoic signal with significant posterior shadowing that often precludes the assessment of calcium thickness (figure 1).35 Surrogate markers for calcium thickness can be used such as the presence of posterior reverberations (correlated with thinner calcium < 0.5 mm) while significant shadowing is suggestive of thicker calcification ( > 1 mm).25 Recently, an IVUS specific scoring system has been found to be useful in predicting stent underexpansion using 4 criteria: calcium arc > 270° for a length of ≥ 5 mm, presence of 360° calcium, presence of calcified nodules, and adjacent vessel diameter of < 3.5 mm. Scores ≥ 2 suggest that calcium modification should be undertaken and therefore operators should aim to measure each of these parameters on IVUS pullbacks.36

Figure 1. Calcium morphology and measurement using intracoronary imaging. A: concentric calcification on optical coherence tomography (OCT); calcium arc of 264°, depth of 0.68 mm, and length of 11 mm - high risk features by OCT for stent underexpansion and plaque preparation is advised. B: concentric calcification; arc 281°, and depth of 0.8 mm. Automatic calcium detection using Ultreon software; degrees of calcium detected outlined by the orange arc surrounding the OCT image. C: eccentric calcium on the OCT; arc < 180 degrees. Note the sharply demarcated borders of calcium that allow the assessment of calcium depth (1.2 mm) D: calcified nodule on the OCT. Significant posterior shadowing is caused by the nodule precluding the assessment of its posterior border. E: concentric calcification on IVUS with an arc of 250° and a length of 9.8 mm. Posterior shadowing and lack of reverberations suggests thick calcium (~1 mm). These features represent a high risk of stent underexpansion. F: concentric calcification on intravascular ultrasound (IVUS) with an arc of 360°. G: eccentric calcification on IVUS with an arc of < 180°. Significant posterior shadowing (blue asterisk). H: calcified nodule on IVUS protruding into the lumen and casting significant posterior acoustic shadowing (blue asterisk). The yellow asterisk (in all OCT images) denotes wire artefact.

Optical coherence tomography

Although significantly more sensitive than angiography OCT is less sensitive compared to the IVUS at detecting coronary calcium. Wang et al. found that ~6% of lesions with IVUS detectable calcium did not show visible calcium on OCT, which was mainly attributed to overlying fibrotic plaque.25 On the OCT, calcium appears as a region of low signal intensity with sharply demarcated borders that facilitate the assessment of calcium depth.26 Fujino et al. demonstrated that calcium arc > 180°, depth > 0.5 mm, and length > 5 mm on the OCT were associated with a higher risk of stent underexpansion and—similar to IVUS—operators should try to analyse each of these parameters.37 Recently, artificial intelligence software has become available (Ultreon OCT system, Abbott, United States), which automatically identifies calcium arc and depth, as well as the external elastic lamina for vessel sizing further simplifying this analysis (figure 1).

In practical terms, therefore, it may be useful to assess the extent of coronary calcification on IVI by considering calcium arc, depth, length, and whether it is superficial or deep as shown on figure 1. Considering the circumferential arc, coronary calcium can be divided into 3 morphological subtypes (figure 1). Eccentric, extending across 2 or less quadrants with an arck < 180°, and concentric, with an arc > 180° and nodular calcification presenting as an eruptive protrusion into the lumen. Calcium can also be divided into superficial (located at < 50% of the depth of the plaque plus media thickness) or deep (located at > 50% of the depth of the plaque plus media thickness).28 Calcium length should be measured on the longitudinal projection on both IVUS and OCT.

Calcium modification

Although there is a lack of clinical trials comparing modification techniques in varying calcium morphologies, consensus in this regard suggests that balloon-based therapies may be effective in eccentric calcification, which is short in length. Ablative and lithotripsy-based therapies may be more useful in concentric calcification or long calcified lesions with lithotripsy being particularly useful in deeper calcium deposits. Nodular calcification presents the greatest challenge; however many advocate for the use of ablative techniques, and some recently presented data suggests lithotripsy may have a role.38 Uncrossable and undilatable lesions may be treated with rotational atherectomy (RA) or excimer laser coronary angioplasty (ELCA). While acknowledging the paucity of data and the lack of head-to-head trials comparing the different techniques available, we have tried to summarize this practice, and the practice at our center, into a simplified calcium modification algorithm that can provide some guidance (figure 2). table 2 summarizes the mechanism of action and specifications for these techniques. The expected results following calcium modification are shown on figure 3.

Table 2. Calcium modification tools: description, mechanism of action, and specifications

Cutting balloons Scoring balloons High-pressure noncompliant NC balloons Rotational atherectomy Orbital atherectomy Excimer LASER Lithotripsy

Technology description

Balloon platform with a number of microblades

Several nitinol wires wrapped around a semi- or noncompliant balloon

Double layered noncompliant balloon

Diamond coated burr capable of atherectomy in a forward motion

Eccentrically mounted diamond coated crown capable of atherectomy in a forward and a backward motion

Concentric or eccentric array of laser fibers.

Uses a mixture of rare gas and halogen to generate brief pulses of high-frequency, short wavelength UV light

Series of emitters encased within a balloon delivery system

Mechanism of action

Controlled incisions into calcium

Controlled incisions into calcium

Super high-pressure dilation with a rated burst pressure of 35 atm (often dilated at ~50 atm)

High speed burr rotation (140-160 000 rpm) results in differential atherectomy of fibrocalcific tissue Additional effect due to burr vibration (+)

Centrifugal force causes the crown to orbit at high speeds (80 or 120 000 rpm) resulting in calcium sanding

Additional effect due to crown vibration (+++)

Disrupts plaque through 3 mechanisms

Photochemical: by breaking carbon bonds between molecules

Photothermal: by the production of thermal energy and vapour bubbles

Photomechanical: by the expansion of vapour bubbles causing plaque disruption

The light energy (fluence) used ranges between 30 mL/mm2 and 80 mL/mm2

Pulse repetition rate is between 25 Hz and 80 Hz

Emitters generate sparks creating a vapour bubble that expands and propagates an acoustic wave through the vessel wall. Causes compressive and decompressive forces when calcium is found resulting in fracture

Sizes available

A number of brands available in sizes ranging from 2.0 mm to 4.0 mm

A number of brands available in sizes that range from 1.75 mm to 4.0 mm

1.5 mm to 4.5 mm balloons

1.25, 1.5, 1.75, 2.0, 2.15, 2.25, 2.38, 2.5 mm burr

1.25 mm crown

0.9 mm, 1.4 mm, 1.7 mm, and 2.0 mm

2.5 mm, 3.0 mm, 3.5 mm, and 4.0 mm diameters

All sizes are 12 mm in length

Guide catheter compatibility


Some balloon sizes are compatible with 5-Fr and 6-Fr systems


6-Fr; 1.25 & 1.5 mm

7-Fr; 1.75 mm

8-Fr; 2.0, 2.15 mm

9-Fr; 2.25, 2.38 mm

10-Fr; 2.50 mm


6-Fr: 0.9 & 1.4 mm

7-Fr: 1.7 mm

8-Fr: 2.0 mm


Wire compatibility

Conventional 0.014 in guidewires

Conventional 0.014 in guidewires

Conventional 0.014 in guidewires

Specialized 0.009 or 0.014 in wire required

Specialized 0.012 or 0.014 in wire required

Viper wire

Conventional 0.014 in guidewires

Conventional 0.014 in guidewires

Other caveats

1:1 balloon: vessel sizing

Rotating the balloon followed by repeat inflation can increase the number of incisions

1:1 balloon: vessel sizing

1:1 balloon: vessel sizing

Burr-to-artery ratio of 0.5 to 0.6

Lubricant available but not mandatory and contraindicated in egg and olive oil allergies

Specific lubricant required which is contraindicated in egg and soy allergies

Catheter-to-artery ratio of 0.5 to 0.6

Requires continuous infusion of saline through the guide catheter

Contrast infusion increases effectiveness but can also increase the risk of thermal damage

1:1 balloon: vessel sizing

Rigorous balloon preparation to remove all air

May require de-airing while being used


Easy to use

Compatible with conventional guidewires

Easy to use

Compatible with conventional guidewires

Easy to use

Compatible with conventional guidewires

Useful in undilatable lesions

May be more useful for nodular calcium than other technologies

Useful in undilatable lesions

May be more useful for nodular calcium than other technologies

Can ablate in both a forward and a backward motion

Produces smaller particles than rotational atherectomy

Easy to use

Compatible with conventional guidewires

Easy to use

Compatible with conventional guidewires

Modifies superficial and deep calcification

No particulate matter created so lower risk of slow flow or no-reflow


May not be sufficient as monotherapy

Bulky profile

May not be sufficient as monotherapy

Bulky profile

Bulky profile

Specialized wire required

Wire bias may result in differential atherectomy.

Ablation in a forward motion only

Cannot maintain a wire in a side branch during atherectomy.

Produces larger particles compared to orbital atherectomy

Distal embolization can result in slow flow or no-reflow

Specialized wire required

Specialized lubrication infusion required

Cannot maintain a wire in a side branch during atherectomy.

Distal embolization can result in slow flow or no-reflow

Set up time

Additional UV protection required

Bulky profile for lesion crossing

80 pulses per catheter may require the use of > 1 catheter to treat long lesions

Potential complications



Slow flow/no reflow



Slow flow/no reflow



Slow flow/no reflow



Burr entrapment

Wire fracture

Slow flow/no reflow

Transient heart block



Crown entrapment

Slow flow/no reflow



Thermal injury



Fr, French; Hz, Hertz; in, inches; NC, noncompliant; rpm, revolutions per minute; UV, ultraviolet.

Figure 2. Calcium modification algorithm. Intravascular imaging (IVI) for lesion assessment is advised prior to undertaking plaque modification. Uncrossable lesions usually require rotational atherectomy or excimer laser coronary angioplasty (ELCA). Crossable lesions with eccentric calcification without high-risk features for stent underexpansion can be treated using noncompliant, cutting or scoring balloons. Concentric calcification or calcium with high-risk features for stent underexpansion can be treated with atherectomy techniques or intravascular lithotripsy (IVL). Nodular calcium can be modified using atherectomy techniques with emerging evidence that IVL may also be effective. Post plaque modification IVI is key for proper plaque modification assessment. Ca, calcium.

Figure 3. Calcium morphologies and results of different modification techniques on intravascular imaging. A: discrete calcium incisions and fracture following cutting balloon (yellow asterisk). B, C: calcium fractures following intravascular lithotripsy on optical coherence tomography and intravascular ultrasound (IVUS) (blue asterisk). Note how reverberations can be seen at fracture points (blue asterisk) on the IVUS due to acoustic waves now being able to pass through the fracture sites. D: results of calcium modification using rotational atherectomy in an uncrossable lesion. A “cored out” appearance can be seen with widening of the lumen and a semilunar appearance in some regions (blue arrow). E: results of calcium modification following orbital atherectomy. The semilunar shape of the orbital atherectomy crown can be seen at the yellow arrows.

Eccentric calcification therapies

Specialized balloon-based technologies

Specialized balloon-based technologies are most commonly used for eccentric calcification although they have some utility in concentric calcification in combination with other techniques. Cutting balloons consist of a number of microblades mounted on a balloon, while scoring balloons consist of a semi-compliant balloon around which several nitinol wires are wrapped. Both aim to make incisions into the calcium to facilitate vessel dilation. The advantage of these technologies is that they anchor to the calcium and are less likely to slip (watermelon seeding phenomenon) thus avoiding dissection of adjacent areas. Although sometimes used interchangeably, a study conducted by Matsukawa et al. using IVI demonstrated better calcium modification and increased luminal gain with cutting balloons vs scoring balloons.39 However, regarding severe calcification, cutting balloons have lower rates of procedural success compared to RA.40 Combining cutting balloons with other technologies may be useful. Observational studies have demonstrated increased luminal gain with cutting balloons following RA compared to conventional balloons or RA alone.41,42

Very high-pressure balloons may be effective to cause calcium fracture in both eccentric and concentric calcification. They are generally not first-line therapies and are most often used in undilatable lesions. They consist of a noncompliant twin-layered balloon with rated burst pressure of ~35 atm. However, in practice they are often dilated at ~50 atm. In a retrospective series of 326 consecutive undilatable lesions, Secco et al. reported angiographic success in > 90% using the OPN high-pressure balloon (OPN NC; SIS Medical AG, Switzerland).43 Calcific lesions with calcium arcs > 270° were more likely to require pressures > 40 atm. More recently, the ISAR-CALC trial randomized lesions with residual stenosis > 30% following standard balloons to receive a scoring balloon or a super high-pressure balloon.44 No differences on OCT defined stent expansion index between groups were found (0.72 vs 0.68; P = .22) nor were there differences in angiographic, procedural, or strategy success. Patients in the super high-pressure balloon group, however, less frequently required further dilation with NC balloons prior to stenting, had larger angiographically assessed minimal lumen diameters, and less residual stenosis compared to those in the scoring balloon cohort. Therefore, super high-pressure balloons play a role in the management of undilatable, but crossable lesions.

Concentric and nodular calcification


Intravascular lithotripsy (IVL) (SHOCKWAVE Medical inc, United States) is a recently introduced technique based on the use of acoustic energy. It consists of a balloon-based delivery system containing a number of emitters that generate short electric sparks. The sparks produce a vapour bubble in the fluid inside the balloon that is dilated to 4 atm. The vapour bubble expands creating an acoustic pressure wave that propagates through the vessel wall causing compression and decompression stress when calcium is encountered resulting in fracture.45 Each short-lived pulse delivers an equivalent of ~50 atm of pressure. Nonrandomized studies to date have demonstrated significant fissuring of both superficial and deep calcium on IVI (figure 3). A pooled analysis of the DISRUPT CAD series of studies has demonstrated procedural success (residual angiographic stenosis ≤ 30%) in > 90% of the lesions.46 Although to date, IVL has been predominantly used in concentric calcium, analysis of angiographically defined eccentric vs concentric calcification suggests similar success in these 2 calcium morphologies.47 Also, recently presented data suggests no differences in minimal stent area on OCT when IVL was used to treat eccentric, concentric, and nodular calcium.38 Although still an off-label indication, a number of cases and series have reported on the use of IVL to treat stent underexpansion due to severe calcification, and calcified neoatherosclerosis.48-51 The use of IVL in a newly deployed but underexpanded stent has not been widely reported and there are theoretical concerns regarding damage to the polymer. Our practice to date has been to use IVL predominantly in concentric calcification while further data is awaited. figure 4 shows a case of plaque modification using OCT-guided IVL.

Figure 4. Case example demonstrating calcium modification using intravascular lithotripsy (IVL) guidance with co-registered optical coherence tomography (OCT) imaging using Ultreon software. A: severely calcified left anterior descending coronary artery stenosis with calcium visible on fluoroscopy (inset), B: OCT revealing concentric calcium; arc 258o and depth of 0.95 mm as identified automatically using the Ultreon software with a length of 18 mm. These parameters suggest a high risk of stent underexpansion. C: proximal and distal landing zones and length of stent required. The distal landing zone external elastic lamina to external elastic lamina (dashed white lines automatically detected by Ultreon system) measures 3.16 mm while, proximally, the external elastic lamina cannot be visualized, and lumen diameter is 2.62 mm. The predicted length of the stent required is 45 mm. D: 3.0 mm x 12 mm IVL balloon (1:1 sizing). Sixty pulses delivered along the calcified lesion. E, F: extensive calcium fracture seen on the OCT after IVL (white arrows). A dissection is also noted (white asterisk). G: stent implantation with a 3.0 mm x 48 mm drug-eluting stent according to the sizing by OCT. Optimized with a 3.0 mm x 12 mm noncompliant balloon. F: final OCT; optimal stent expansion (> 90%), no malapposition or complications (eg, dissection) at the proximal and distal landing sites.

Rotational atherectomy

RA (Rotablator, Boston Scientific, United States) uses a diamond-tipped burr that rotates at 140-180 000 rpm Resulting in the differential ablation of calcified tissue while avoiding disruption of healthy elastic tissue. Ablation occurs only in a forward motion. A specialized wire (RotaWire Floppy or RotaWire Extra Support, Boston Scientific, United States) is required and the burr size should not exceed 0.5-0.6 times the size of the vessel. Previously, the infusion of nitroglycerin, verapamil or heparin were advocated to mitigate the effects of debris embolization while temporary pacing wire insertion or aminophylline infusion were used to combat bradycardia particularly when performing RA in the right coronary artery. However, changes to RA techniques have reduced these complications. Aggressive debulking with RA has been replaced by the use of shorter runs (10-15 seconds), a pecking motion of the burr, smaller burr sizes, and resting periods to allow clearance of embolized particles. On IVI, a smoothing out of the calcium can be seen sometimes with a semilunar shape from where the burr has ablated (figure 3).

The ROTAXUS trial randomized 240 patients with calcified CAD to RA or conventional therapy prior to drug-eluting stenting.52 Both procedural success and luminal gain (1.56 mm vs 1.44 mm, P < .01) were higher in the RA group at the index procedure. However, higher late luminal loss in the RA group was seen at 9 months (0.44 mm vs 0.31 mm, P = .04). Furthermore at 2-year follow-up no differences were seen between groups regarding major adverse cardiovascular events, myocardial infarction, target lesion revascularization or target vessel revascularization (P > .05 for all comparisons).53 The PREPARE-CALC study examined RA vs modified balloons (cutting or scoring) in the treatment of severely calcified disease. Similar to the ROTAXUS trial, increased strategy success was seen in the RA arm vs the modified balloon arm (98% vs 81%, P = .0001) mainly attributed to a higher crossover rate in the modified balloon group (10% of modified balloon group).40 However, improved strategy success in the RA arm did not translate into differences in clinical or angiographic outcomes at 9 months.40 This may be partially explained by the fact that final stent expansion as seen on OCT was not different between groups (73.5% vs 73.1% for modified balloons vs RA respectively, P = .85).54

Combinations of complementary calcium modification therapies are increasingly being used. A study of 92 patients conducted by Tang et al. found greater decrease in percent stenosis (54.5% to 36.1% vs 55.7% to 46.9%, P < .001), and greater stent expansion (71.7% vs 54.5%) with RA followed by cutting balloon compared to RA alone.41 Similarly, Amemiya et al. found greater calcium fracture and stent expansion (78.9% vs 66.7%, P < .01) on OCT with cutting balloon vs standard balloon angioplasty after RA.42 Additionally, there have been numerous case reports regarding the use of IVL following RA with good effect.55,56 Larger scale observational and randomized studies are required to determine if improved longer term outcomes can be achieved by these (and other) combinations. In practical terms and in our own clinical practice, RA plays a role in uncrossable and undilatable lesions, and severe concentric calcification (figure 2) often in combination with other techniques.

Orbital atherectomy

OA (DIAMONDBACK 360 orbital atherectomy system, Cardiovascular systems Inc., United States) consists of a diamond coated crown that uses centrifugal force to orbit resulting in preferential calcium sanding while flexing away from healthy elastic tissue. It requires a dedicated wire (ViperWire advance), and lubricant infusion (ViperSlide both Cardiovascular systems Inc., United States) during ablation. The 1.25 mm crown orbits at 1 of 2 speed settings (80 or 120 000 rpm), which results in widening or narrowing of the orbital arc. Unlike RA, the OA can ablate both in forward and backward motion, and requires slow smooth movements (~1mm/second). Atherectomy runs should be ≤ 30 seconds with resting periods to allow clearance of debris. IVI following OA demonstrates smoothed out calcium often with a visible arc or semilunar shape where sanding occurred (figure 3). The nonrandomized ORBIT I and II studies examined the safety and effectiveness of OA finding a reduction in percentage diameter stenosis to ≤ 50% in > 98% of the lesions.57,58 Significant dissection occurred in 2.3% of the cases. However, the rate of other complications such as perforation, slow, and no-reflow was low and < 1%.58 The 3-year follow-up of the ORBIT II study demonstrated cumulative rates of major adverse cardiovascular events and target lesion revascularization of 23.5%, and 7.8%, respectively.59 The single arm prospective COAST study examined a modified OA system with a distal microcrown to improve penetration with a reduction in percentage diameter stenosis to ≤ 50% in > 99% of the lesions.60 There are currently no randomized trials comparing OA to other forms of calcium modification. However, a small OCT study suggested deeper calcium modification with OA vs RA,61 and a meta-analysis of observational studies found no difference in procedural complications or 30-day events including death, myocardial infarction, and target vessel revascularization between OA and RA.62 However, although more data is required, our practice is to use OA over RA in larger vessels with concentric or nodular calcium. figure 5 demonstrates an example of OA plaque modification and table 3 summarizes the current data for both OA and RA.

Table 3. Summary of the main prospective studies examining outcomes in RA and OA techniques

Technique Study name Design Number of participants Procedural outcomes Short-to-medium term outcomes Long-term outcomes

Rotational atherectomy

ROTAXUS study52,53

Randomized controlled trial


• 120 RA

• 120 Standard therapy (Std Tx)

Strategy success

• RA, 92.5% vs Std Tx, 83.3%, P = .03

Acute luminal gain

• RA, 1.56mm vs Std Tx, 1.44, P < .01


• RA, 3.3% vs Std Tx, 3.3%, P = .99


• RA, 1.7% vs Std Tx, 0.8%, P = .56

Slow/no flow

• RA, 0% vs Std Tx, 0.8%, P = .32

9-month out comes

In-stent LLL

• RA, 0.44mm vs Std Tx, 0.31, P = .04


• RA, 5.0% vs Std Tx, 5.8%, P = .78.


• RA, 6.7% vs Std Tx, 5.8%, P = .79


• RA, 16.7% vs Std Tx, 18.3%, P = .73


• RA, 24.2% vs Std Tx, 28.3%, P = .46.


• RA, 11.7% vs Std Tx, 12.5%, P = .84

2-year outcomes


• RA, 29.4% vs Std Tx, 34.3%, P = .47


• RA, 8.3% vs Std Tx, 7.4%, P = 1.00)

Myocardial infarction

• RA, 8.3% vs Std Tx, 6.5%, P = .80),


• RA, 13.8% vs Std Tx, 16.7%, P = .58


• RA, 19.3% vs Std Tx, 22.2%, P = .62)


Randomized controlled trial


• 100 RA

• 100 MB

Strategy success

• RA, 98% vs MB, 81%, P = .0001


• RA, 3% vs MB, 7%, P = .33


• RA, 4% vs MB, 2%, P = .68

Slow/no flow

• RA, 2% vs MB, 0%, P = .49

9 months

In-stent LLL

• RA, 0.22 vs MB, 0.16mm, P = .21


• RA, 2% vs MB, 2%, P = 1.00


• RA, 3% vs MB, 6%, P = .50


• RA, 2% vs MB, 7%, P = .17

Definite/probable stent thrombosis

• RA, 0% vs MB, 0%, P = 1.00


• RA, 6% vs MB, 8%, P = .78

Orbital atherectomy


Prospective non-randomized


• Device success, 98%,

• Procedural success, 94%

• Dissection, 12%

• Perforation, 2%

• In-hospital MACE, 4%


• 30-days, 6%

• 6 months, 8%


Prospective multicentre non-randomized


• Procedural success, 88.9%

• Angiographic success, 91.4%

• Severe dissection, 2.3%

• Perforation, 0.9%

• Slow/no flow, 0.2%

• In-hospital MACE, 9.8%


• 30-day, 10.4%


• MACE, 23.5%

• Cardiac death, 6.7%

• MI, 11.2%

• TVR, 10.2%

• TLR, 7.8%


Prospective multicentre single-arm


• Procedural success, 85%

• In-hospital MACE, 14%

• Dissection, 2%

• Perforation, 2%

• Slow/no flow, 2%


• 30-day, 15%

1 year

• MACE, 22.2%

MACE, major adverse cardiovascular events; MB, modified balloons; MI, myocardial infarction; OA, orbital atherectomy; RA, rotational atherectomy; Std Tx, standard therapy, RS, residual stenosis; TIMI, Thrombolysis in Myocardial Infarction; TLR, target lesion revascularization; TVR, target vessel revascularization.


• Strategy success: Successful stent delivery, < 20% in-stent RS, TIMI grade-3 flow without crossover or stent failure

• Device success: < 50% RS following OA without device malfunction

• Angiographic success: stent delivery with RS < 50%


• MACE: MI, TVR, and cardiac death


• Procedural success: < 20% in-stent RS

• MACE: cardiac death, MI or TLR


• Procedural success: stent delivery with a < 50% RS without in-hospital MACE.

• MACE: MI, TVR, and cardiac death


• MACE: cardiac death, MI or TVR

Figure 5. Calcium modification using orbital atherectomy guided by co-registered optical coherence tomography (OCT) imaging. A: severely calcified mid-left anterior descending coronary artery stenosis B: OCT showing severe circumferential calcification; arc of ~270°, depth of 0.7 mm, and length > 5 mm suggesting a high risk of stent underexpansion according to OCT criteria. Distal and proximal reference luminal diameters of 2.5 mm, and 3.25 mm, respectively, with a predicted stent length of 33 mm. C: orbital atherectomy (yellow arrow) using the DIAMONDBACK 360 orbital atherectomy system, and a 1.25 mm crown advanced at 1 mm/s. Sanding/atherectomy was performed in a forward and a backward motion. Dynamic road mapping was also used to guide the procedure (bottom left). D: smoothed out appearance after orbital atherectomy. Image shows that calcium ‘cap’ has been greatly reduced by the sanding effect of orbital atherectomy (OA). A semilunar shape can be seen as an effect of the orbiting crown (white arrows). E: post-OA angiography demonstrating significantly reduced percent stenosis. F: implantation of a 2.5 mm x 36 mm drug-eluting stent with proximal optimization using a 3.5 mm x 10 mm noncompliant balloon (inset). G: final co-registered OCT post-OA, and stenting demonstrating adequate stent expansion and apposition without complications.

Excimer laser coronary angioplasty

Excimer laser coronary angioplasty (ELCA) uses a mixture of rare gas and halogen to generate brief pulses of high-frequency ultraviolet light which disrupts atherosclerotic plaque through 3 mechanisms: photochemical by breaking down the carbon bonds between the molecules, photothermal due to the production of heat and vapour bubbles causing cell rupture, and photomechanical by the expansion of vapour bubbles causing the disruption of the plaque. Fluence (energy measured in mJ/mm2), and pulse frequency can be altered to increase its effectiveness. Constant saline infusion is advised to avoid thermal injury. Also, the short wavelength (~308 nm) of ultraviolet light used reduces the depth of penetration, thus avoiding damage to healthy tissues. Evidence on the use of ELCA in calcified CAD is limited. A prospective multicentre study of 100 uncrossable/undilatable lesions demonstrated technical success in 92% of lesions63 while a more recent prospective multicentre study of 126 uncrossable lesions demonstrated success in ~82% of cases.64 However, severe calcification was significantly associated with ELCA failure. In the setting of in-stent restenosis, more calcium fracture on OCT was seen in the ELCA vs conventional treatment group.65 Given the paucity of large-scale studies and considering the data available to date, ELCA has a relatively niche role predominantly for the management of uncrossable lesions although we prefer to use RA as the first-line ablative therapy in this circumstance.


Calcified CAD continues to present a barrier for successful PCI. Furthermore, our ageing population suggests that the proportion of patients with calcified CAD who will present for PCI is likely to increase. Its presence is associated not just with poorer acute outcomes, but also with more adverse events at long-term follow-up. Stent underexpansion is one of the most powerful predictors of stent failure, and often occurs in the presence of significant coronary calcification. Identifying the presence of coronary calcium is key in planning a PCI, and is more accurately done using IVI. A number of technologies with different mechanisms of action are now available to modify coronary calcium although head-to-head comparisons between these techniques are lacking. Nonetheless, we propose a simplified calcium modification algorithm based on IVI findings that is currently used at our center. Future studies should aim to compare techniques and elucidate the best technique combinations to ensure improved outcomes in these complex patients.


None whatsoever.


A. McInerney: concept, design, and drafting of the manuscript. J. Escaned: contributed clinical images, and was involved in the critical review of the manuscript. N. Gonzalo: concept, design, drafting, and critical review of the manuscript. Contributed clinical images.


N. Gonzalo reports consultancy and speaker fees from Abbott and Boston Scientific. The remaining authors reported no conflicts of interest pertaining to the current publication.


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12. Detrano R, Guerci AD, Carr JJ, et al. Coronary calcium as a predictor of coronary events in four racial or ethnic groups. N Engl J Med. 2008;358:1336-1345.

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14. Motoyama S, Kondo T, Sarai M, et al. Multislice computed tomographic characteristics of coronary lesions in acute coronary syndromes. J Am Coll Cardiol. 2007;50:319-326.

15. Jin HY, Weir-McCall JR, Leipsic JA, et al. The Relationship Between Coronary Calcification and the Natural History of Coronary Artery Disease. JACC Cardiovasc Imaging. 2021;14:233-242.

16. Kobayashi Y, Okura H, Kume T, et al. Impact of target lesion coronary calcification on stent expansion. Circ J. 2014;78:2209-2214.

17. Genereux P, Madhavan MV, Mintz GS, et al. Relation between coronary calcium and major bleeding after percutaneous coronary intervention in acute coronary syndromes (from the Acute Catheterization and Urgent Intervention Triage Strategy and Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction Trials). Am J Cardiol. 2014;113:930-935.

18. Hendry C, Fraser D, Eichhofer J, et al. Coronary perforation in the drug-eluting stent era: incidence, risk factors, management and outcome: the UK experience. EuroIntervention. 2012;8:79-86.

19. Konigstein M, Madhavan MV, Ben-Yehuda O, et al. Incidence and predictors of target lesion failure in patients undergoing contemporary DES implantation-Individual patient data pooled analysis from 6 randomized controlled trials. Am Heart J. 2019;213:105-111.

20. Guedeney P, Claessen BE, Mehran R, et al. Coronary Calcification and Long-Term Outcomes According to Drug-Eluting Stent Generation. JACC Cardiovasc Interv. 2020;13:1417-1428.

21. Kawashima H, Serruys PW, Hara H, et al. 10-Year All-Cause Mortality Following Percutaneous or Surgical Revascularization in Patients With Heavy Calcification. JACC Cardiovasc Interv. 2022;15:193-204.

22. Knez A, Becker A, Leber A, et al. Relation of coronary calcium scores by electron beam tomography to obstructive disease in 2,115 symptomatic patients. Am J Cardiol. 2004;93:1150-1152.

23. Budoff MJ, Diamond GA, Raggi P, et al. Continuous probabilistic prediction of angiographically significant coronary artery disease using electron beam tomography. Circulation. 2002;105:1791-1796.

24. Mintz GS, Popma JJ, Pichard AD, et al. Patterns of calcification in coronary artery disease. A statistical analysis of intravascular ultrasound and coronary angiography in 1155 lesions. Circulation. 1995;91:1959-1965.

25. Wang X, Matsumura M, Mintz GS, et al. In Vivo Calcium Detection by Comparing Optical Coherence Tomography, Intravascular Ultrasound, and Angiography. JACC Cardiovasc Imaging. 2017;10:869-879.

26. Tearney GJ, Regar E, Akasaka T, et al. Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation. J Am Coll Cardiol. 2012;59:1058-1072.

27. Raber L, Mintz GS, Koskinas KC, et al. Clinical use of intracoronary imaging. Part 1: guidance and optimization of coronary interventions. An expert consensus document of the European Association of Percutaneous Cardiovascular Interventions. Eur Heart J. 2018;39:3281-3300.

28. Mintz GS, Nissen SE, Anderson WD, et al. American College of Cardiology Clinical Expert Consensus Document on Standards for Acquisition, Measurement and Reporting of Intravascular Ultrasound Studies (IVUS). A report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2001;37:1478-1492.

29. Gao XF, Ge Z, Kong XQ, et al. 3-Year Outcomes of the ULTIMATE Trial Comparing Intravascular Ultrasound Versus Angiography-Guided Drug-Eluting Stent Implantation. JACC Cardiovasc Interv. 2021;14:247-257.

30. Hong SJ, Mintz GS, Ahn CM, et al. Effect of Intravascular Ultrasound-Guided Drug-Eluting Stent Implantation: 5-Year Follow-Up of the IVUS-XPL Randomized Trial. JACC Cardiovasc Interv. 2020;13:62-71.

31. Kinnaird T, Johnson T, Anderson R, et al. Intravascular Imaging and 12-Month Mortality After Unprotected Left Main Stem PCI: An Analysis From the British Cardiovascular Intervention Society Database. JACC Cardiovasc Interv. 2020;13:346-357.

32. Mc Inerney A, Escaned J, Gonzalo N. Online Co-Registration Of IVUS and OCT. Minerva Cardiol Angiol. 2021;69:641-654.

33. Pu J, Mintz GS, Biro S, et al. Insights into echo-attenuated plaques, echolucent plaques, and plaques with spotty calcification: novel findings from comparisons among intravascular ultrasound, near-infrared spectroscopy, and pathological histology in 2,294 human coronary artery segments. J Am Coll Cardiol. 2014;63:2220-2233.

34. Kim SW, Mintz GS, Lee WS, et al. DICOM-based intravascular ultrasound signal intensity analysis: an Echoplaque Medical Imaging Bench study. Coron Artery Dis. 2014;25:236-241.

35. Mintz GS. Intravascular imaging of coronary calcification and its clinical implications. JACC Cardiovasc Imaging. 2015;8:461-471.

36. Zhang M, Matsumura M, Usui E, et al. Intravascular Ultrasound-Derived Calcium Score to Predict Stent Expansion in Severely Calcified Lesions. Circ Cardiovasc Interv. 2021;14:e010296.

37. Fujino A, Mintz GS, Matsumura M, et al. A new optical coherence tomography-based calcium scoring system to predict stent underexpansion. EuroIntervention. 2018;13:e2182-e2189.

38. Ali Z, Price M, Maehara A, Lansky A. New Insights on the Consistency of Coronary IVL Data. Proceedings of Transcatheter Cardiovascular Therapeutics; 2021 05/11/2021. Available online: https://tct2021.crfconnect.com/ondemand/world-connect/86455. Accessed 12 Dec 2021.

39. Matsukawa R, Kozai T, Tokutome M, et al. Plaque modification using a cutting balloon is more effective for stenting of heavily calcified lesion than other scoring balloons. Cardiovasc Interv Ther. 2019;34:325-334.

40. Abdel-Wahab M, Toelg R, Byrne RA, et al. High-Speed Rotational Atherectomy Versus Modified Balloons Prior to Drug-Eluting Stent Implantation in Severely Calcified Coronary Lesions. Circ Cardiovasc Interv. 2018;11:e007415.

41. Tang Z, Bai J, Su SP, et al. Aggressive plaque modification with rotational atherectomy and cutting balloon for optimal stent expansion in calcified lesions. J Geriatr Cardiol. 2016;13:984-991.

42. Amemiya K, Yamamoto MH, Maehara A, et al. Effect of cutting balloon after rotational atherectomy in severely calcified coronary artery lesions as assessed by optical coherence tomography. Catheter Cardiovasc Interv. 2019;94:936-944.

43. Secco GG, Buettner A, Parisi R, et al. Clinical Experience with Very High-Pressure Dilatation for Resistant Coronary Lesions. Cardiovasc Revasc Med. 2019;20:1083-1087.

44. Rheude T, Rai H, Richardt G, et al. Super high-pressure balloon versus scoring balloon to prepare severely calcified coronary lesions: the ISAR-CALC randomised trial. EuroIntervention. 2021;17:481-488.

45. Kereiakes DJ, Virmani R, Hokama JY, et al. Principles of Intravascular Lithotripsy for Calcific Plaque Modification. JACC Cardiovasc Interv. 2021;14:1275-1292.

46. Kereiakes DJ, Di Mario C, Riley RF, et al. Intravascular Lithotripsy for Treatment of Calcified Coronary Lesions: Patient-Level Pooled Analysis of the Disrupt CAD Studies. JACC Cardiovasc Interv. 2021;14:1337-1348.

47. Blachutzik F, Honton B, Escaned J, et al. Safety and effectiveness of coronary intravascular lithotripsy in eccentric calcified coronary lesions: a patient-level pooled analysis from the Disrupt CAD I and CAD II Studies. Clin Res Cardiol. 2021;110:228-236.

48. Salazar C, Escaned J, Tirado G, Gonzalo N. Intravascular lithotripsy for recurrent restenosis caused by severe calcific neoatherosclerosis. EuroIntervention. 2020;16:e351-e352.

49. Salazar C, Escaned J, Tirado G, Gonzalo N. Undilatable Calcific Coronary Stenosis Causing Stent Underexpansion and Late Stent Thrombosis: A Complex Scenario Successfully Managed With Intravascular Lithotripsy. JACC Cardiovasc Interv. 2019;12:1510-1512.

50. Yeoh J, Cottens D, Cosgrove C, et al. Management of stent underexpansion using intravascular lithotripsy-Defining the utility of a novel device. Catheter Cardiovasc Interv. 2021;97:22-29.

51. Ali ZA, McEntegart M, Hill JM, Spratt JC. Intravascular lithotripsy for treatment of stent underexpansion secondary to severe coronary calcification. Eur Heart J. 2020;41:485-486.

52. Abdel-Wahab M, Richardt G, Joachim Buttner H, et al. High-speed rotational atherectomy before paclitaxel-eluting stent implantation in complex calcified coronary lesions: the randomized ROTAXUS (Rotational Atherectomy Prior to Taxus Stent Treatment for Complex Native Coronary Artery Disease) trial. JACC Cardiovasc Interv. 2013;6:10-19.

53. de Waha S, Allali A, Buttner HJ, et al. Rotational atherectomy before paclitaxel-eluting stent implantation in complex calcified coronary lesions: Two-year clinical outcome of the randomized ROTAXUS trial. Catheter Cardiovasc Interv. 2016;87:691-700.

54. Hemetsberger R, Gori T, Toelg R, et al. Optical Coherence Tomography Assessment in Patients Treated With Rotational Atherectomy Versus Modified Balloons: PREPARE-CALC OCT. Circ Cardiovasc Interv. 2021;14:e009819.

55. Kaur N, Pruthvi CR, Sharma Y, Gupta H. Rotatripsy: synergistic effects of complementary technologies: a case report. Eur Heart J Case Rep. 2021;5:ytab083.

56. Gonzálvez-García A, Jiménez-Valero S, Galeote G, et al. “RotaTripsy: Combination of rotational atherectomy and intravascular lithotripsy in heavily calcified coronary lesions: A case series”. Cardiovasc Revasc Med. 2022;35:179-184.

57. Parikh K, Chandra P, Choksi N, Khanna P, Chambers J. Safety and feasibility of orbital atherectomy for the treatment of calcified coronary lesions: the ORBIT I trial. Catheter Cardiovasc Interv. 2013;81:1134-1139.

58. Chambers JW, Feldman RL, Himmelstein SI, et al. Pivotal trial to evaluate the safety and efficacy of the orbital atherectomy system in treating de novo, severely calcified coronary lesions (ORBIT II). JACC Cardiovasc Interv. 2014;7:510-518.

59. Lee M, Genereux P, Shlofmitz R, et al. Orbital atherectomy for treating de novo, severely calcified coronary lesions: 3-year results of the pivotal ORBIT II trial. Cardiovasc Revasc Med. 2017;18:261-264.

60. Redfors B, Sharma SK, Saito S, et al. Novel Micro Crown Orbital Atherectomy for Severe Lesion Calcification: Coronary Orbital Atherectomy System Study (COAST). Circ Cardiovasc Interv. 2020;13:e008993.

61. Kini AS, Vengrenyuk Y, Pena J, et al. Optical coherence tomography assessment of the mechanistic effects of rotational and orbital atherectomy in severely calcified coronary lesions. Catheter Cardiovasc Interv. 2015;86:1024-1032.

62. Goel S, Pasam RT, Chava S, et al. Orbital atherectomy versus rotational atherectomy: A systematic review and meta-analysis. Int J Cardiol. 2020;303:16-21.

63. Bilodeau L, Fretz EB, Taeymans Y, et al. Novel use of a high-energy excimer laser catheter for calcified and complex coronary artery lesions. Catheter Cardiovasc Interv. 2004;62:155-161.

64. Ojeda S, Azzalini L, Suarez de Lezo J, et al. Excimer laser coronary atherectomy for uncrossable coronary lesions. A multicenter registry. Catheter Cardiovasc Interv. 2021;98:1241-1249.

65. Lee T, Shlofmitz RA, Song L, et al. The effectiveness of excimer laser angioplasty to treat coronary in-stent restenosis with peri-stent calcium as assessed by optical coherence tomography. EuroIntervention. 2019;15:e279-e288.

* Corresponding author:

E-mail address: nieves_gonzalo@yahoo.es (N. Gonzalo).


Invasive coronary angiography is the standard approach in the routine clinical practice. Intracoronary imaging modalities provide real-time images of intracoronary anatomy. On this basis, optical coherence tomography and intravascular ultrasound have a positive impact on diagnosis and percutaneous coronary intervention. This summary provides an insight on these imaging modalities for the interventional and clinical cardiologist with the currently available evidence.

Keywords: Intravascular ultrasound. Optical coherence tomography. Invasive coronary angiography.


La coronariografía es el método de elección para el estudio de la anatomía coronaria en la práctica clínica diaria. Las diferentes modalidades de imagen intracoronaria permiten valorar en tiempo real la anatomía de la pared arterial coronaria. Sobre esta base, la tomografía de coherencia óptica y la ecografía intravascular tienen un impacto positivo en el diagnóstico y en el intervencionismo percutáneo. La presente revisión proporciona un resumen de las técnicas de imagen intracoronaria basadas en la evidencia actual disponible.

Palabras clave: Ecografía intravascular. Tomografía de coherencia óptica. Coronariografía.

Abbreviations CA: coronary angiography. CTO: chronic total coronary occlusion. ICI: intracoronary imaging. IVUS: intravascular ultrasound. LMCAD: left main coronary artery disease. MACE: major adverse cardiovascular events. OCT: optical coherence tomography. PCI: percutaneous coronary intervention.


Coronary artery disease is still the leading cause of death across the world and can manifest through a wide range of presentations given its dynamic nature.1 Coronary angiography (CA) is the gold standard approach to assess the presence and severity of coronary artery disease. However, it is limited by qualitative assessment although improvements have been made such as the development of quantitative coronary angiography.2 New imaging modalities for coronary assessment have emerged over the last few decades to improve patient outcomes.3

Intracoronary imaging (ICI) modalities provide an in-depth understanding of the aspects that contribute to the pathogenesis of coronary artery disease, but also help us guide the decision-making process. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) produce real-time cross-sectional images of the coronary artery. Data from clinical studies have suggested improved outcomes during complex ICI-guided percutaneous coronary interventions (PCI).4,5 Both the American and the European clinical guidelines on myocardial revascularization allocate a Class II recommendation—American College of Cardiology/American Heart Association: Class IIa6 and European Society of Cardiology: Class IIa—to IVUS–guided PCI,7 being the OCT-guided PCI an alternative with the exception of ostial left main coronary artery disease.6,7 However, its use is still uneven worldwide.

This review seeks to summarize the evidence available to portray all the potential advantages and downsides of these 2 catheter-based imaging modalities in the routine clinical practice.



IVUS catheters are rapid exchange catheters that have a piezoelectric crystal that produces soundwaves through transducers when electrically excited. Soundwaves propagate through the different tissues reflecting on the surfaces according to the acoustic properties of the tissue. These returned soundwaves are formatted into a grayscale image with dynamic contrast resolution. This modality allows the interventional cardiologist to evaluate the integrity of the vessel wall, characterize tissue composition, and tackle PCI challenges (stent malapposition and underexpansion).8

The quality of the images depends on the soundwave, transducer, and tissue properties. The resulting image resolution is greater at shorter distances (near-field), but it appears less clear in the deep fields (far-field) due to beam scattering. Flow properties also make it more difficult to distinguish the lumen from the tissues. Mechanical or rotational catheters work at 40-60 MHz frequencies, as opposed to electronic ones that operate at 20 MHz frequencies and have greater axial and lateral resolution. Overall, the best images are obtained when the catheter is coaxial to the vessel, the beam is perpendicular to the lesion, and with clear lumens.8,9

IVUS image acquisition should be routinely performed with IV anticoagulation and intracoronary nitrates to prevent device-related complications.5 Vessel interrogation can be performed with manual or automatic pullback starting, at least, 10 mm distal to the target lesion until the aorta or the guiding catheter can be seen. In the case of aorto-ostial lesions, the guiding catheter must be disengaged to unmask ostial lesions. Automatic pullbacks have the advantage of providing measurements of lesion length, which is estimated with the average time and pullback speed. Multiple lesions are considered when distance is > 5 mm within the same coronary segment. However, spatial orientation is a major limitation.8,9 The main features of IVUS are shown on table 1 and table 2.

Table 1. General characteristics of intracoronary imaging modalities

Intracoronary imaging modality Source of image Frequency (Mhz) Wavelength (µm) Minimal guide catheter (Fr) Axial resolution (µm) Lateral resolution (µm) Tissue penetration (mm) Pullback length (mm) Pullback speed (mm/sec)
IVUSa Ultrasound 20-60 40-50 5 20-170 50-260 3-8 100 0.5-10
OCTb Infrared light NA 1.3 5 15-20 20-40 1-3 75 10-40
Hybrid (OCT/IVUS)c Ultrasound and Infrared light 40 1.3 5 200/15 200/30 3-8 100-150 0.5-40

IVUS, intravascular ultrasound; OCT, optical computed tomography; NA, not applicable.

a Includes OptiCross (Boston Scientific, United States), Volcano (Philips, United States), Infraredx (Burlington, United States), ACIST CVi (ACIST, United States), and Fastview (Terumo, Japan).

b Includes OPTIS (Abbott Vascular, United States), and Lunawave (Terumo, Japan).

c Includes Novasight Hybrid (Conavi Medical, Canada), and Dual Sensor (Terumo, Japan).

Table 2. Main advantages and drawbacks of intracoronary imaging modalities

Intravascular ultrasound Optical computed tomography
• More penetration capabilities, capable of assessing plaque volume and deeper plaques.
• Better suited for CTO, aorto-ostial junction, LMCAD, and stent sizing assessment.
• Does not require contrast.
• Higher resolution, fewer artifacts, and facilitates the identification of subtle details
• More user friendly.
• Capable of assessing calcium thickness.
• Better suited for strut and thrombus evaluation.
• Lower resolution.
• Requires anticoagulation and additional time.
• Image interpretation requires experience and expertise.
• Cannot penetrate calcium or adequately evaluate thrombi.
• Expensive.
• Less penetration capabilities, cannot adequately evaluate ostial lesions.
• Requires anticoagulation and additional time.
• Image acquisition requires blood clearance through contrast or other means.
• Image interpretation requires experience and expertise.
• Expensive.

CTO, chronic total coronary occlusions; LMCAD, left main coronary artery disease.

Efforts to explore the potential benefits of IVUS over CA have been reported over the years with promising results. In a recent meta-analysis of 27 610 patients that compared IVUS-guided PCI vs CA-guided PCI, IVUS was associated with less cardiac death (risk ratio [RR], 0.63; 95% confidence interval [95%CI], 0.54–0.73), and PCI-related complications. Similarly, the risk of myocardial infarction (RR, 0.71; 95%CI, 0.58–0.86), target lesion revascularization (RR, 0.81; 95%CI, 0.70–0.94), and stent thrombosis (RR, 0.57; 95%CI, 0.41–0.79) was lower with IVUS-guided PCI.10

Optical coherence tomography

OCT image generation is based on infrared light (1.3 µm wavelength). Compared to IVUS, this imaging modality provides greater axial resolution (10-20 µm vs 50-150 µm) with limited soft tissue penetration (1-2 mm vs 5-6 mm except for calcium evaluation).3,4,11

Current devices are 5-Fr compatible through a rapid exchange system that also allows automatic pullbacks with angiography co-registration and automatic lumen measurements and calcium detection. The quality of the images depends on the interaction of light with the surrounding tissues (echo-time delay). As such, light reflection, refraction, and attenuation (absorption) determine the final image resolution. Metal devices and fibrous plaques are considered strong reflectors while low reflectors are calcium and necrotic cores (lipid-rich). Red blood cells cause light scattering that requires contrast washout causing the appearance of a “pseudo-thrombus” image with poor blood clearance.

OCT imaging is also routinely performed with IV anticoagulation and intracoronary nitrates to prevent complications. The study of the vessel begins 10 mm distal to the target lesion, the catheter is then purged with contrast, and an automatic pullback with co-registration (if available) is performed. The average pullback speed of 10-40 mm/s usually allows a single bolus injection of contrast to achieve a blood-free environment.12 The general OCT features are shown on table 1 and table 2.

Compared to the CA-guided PCI, observational studies have suggested a potential benefit of OCT-guided PCI with lower rates of major adverse cardiovascular events (MACE) and stent-related complications.13 Furthermore, the OCT provides more reliable and reproducible images with less inter-observer variability compared to the IVUS. In this regard, the OCT may be superior to assess stent and lumen diameters.14,15


Acute coronary syndromes

Acute coronary syndromes are mostly caused by coronary thrombosis due to plaque rupture, plaque erosion or an eruptive calcified nodule.16 Accurate diagnosis may have prognostic implications. The rupture of the plaque is associated with a greater rate of no-reflow and distal embolization. Plaque erosion can be conservatively managed in non-critical stenoses. Calcified nodules are associated with a higher rate of stent restenosis and thrombosis17 (figure 1).

Figure 1. Stent thrombosis. A: filling defect (arrowhead) in the mid left anterior descending coronary artery on the right oblique anterior projection. B: co-registration of optical coherence tomography and angiography. C: OCT cross-sectional image showing non-occlusive stent thrombosis (white asterisk). GW, guidewire; OCT, optical coherence tomography; SS, stent struts.

The OCT is often used for the perioperative identification of culprit lesions after careful evaluation of the morphological characteristics of the fibrous cap.18 The plaque classification algorithm through OCT classifies plaques based on the state of fibrous caps, thereby showing an intact fibrous cap in plaque erosion, a disrupted cap as the hallmark of a ruptured plaque or a calcified nodule. The OCT can also determine thrombus burden, but is not necessary to ascertain the culprit lesion. However, a recent publication that compared near infrared spectroscopy combined with IVUS to OCT in 276 patients found that the former can accurately characterize culprit lesions after the characterization of calcium, plaque cavity, and the maximum lipid core burden index with 93% and 100% sensitivity and specificity, respectively.19

Moreover, data supports the preference of ICI-guided PCI to improve outcomes in the management of acute coronary syndrome. A meta-analysis of 26 610 patients reported a net benefit of IVUS regardless of the presence of acute coronary syndrome with a lower rate of MACE (RR, 0.57; 95%CI, 0.41-0.79) compared to the CA-guided PCI.10 Similarly, an observational Korean registry of 11 731 patients treated with primary PCI reported a lower rate of cardiac death, target vessel reinfarction, and target lesion revascularization with either IVUS- or OCT-guidance.20

Bifurcated lesions

Coronary bifurcation lesions are found in 15% to 20% of all patients treated with PCI.21 The main challenge when treating bifurcation lesions is selecting the right PCI strategy to avoid target lesion failure or side-branch occlusion. The importance of careful evaluation is evident with the distal left main coronary artery disease (LMCAD). The European Bifurcation Club recommends intracoronary imaging to treat bifurcated lesions.22

The risk of side-branch compromise can be diminished with both the IVUS and the OCT by selecting the proper stent (type and size), landing zone, and evaluation of post-PCI results (stent expansion and apposition; distal dissection). Intracoronary imaging can identify a “spiky” carina in cases of distal LMCAD, which has been associated with restenosis due to carina shift. Also, some predictors of side-branch compromise with IVUS (minimum lumen area of side-branch and plaque burden)19 and OCT (angle < 50º and branching point to carina tip length < 1.70 mm)23 have been reported.

Also, both imaging modalities can be used for stent sizing in bifurcation lesions; however, areas with high plaque burden or lipid plaques where both imaging modalities are useful should be avoided as landing zones. Overall, ICIs are also useful to treat bifurcations with PCI since they evaluate side-branch wire entry, calcification, lesion length, and post-stent-related complications that may interfere with the clinical outcomes.22 Two randomized control trials are currently evaluating the role of OCT in patients with bifurcated lesions (NCT03171311; NCT03507777).

Coronary artery calcification

Coronary artery calcification increases PCI complexity by impairing stent deployment, expansion, and apposition, which in turn increases the risk of stent thrombosis and restenosis.24 CA can detect—with a low-to-moderate sensitivity—the presence of coronary artery calcification with severe cases being visible without cardiac motion and contrast injection.25

Calcified plaques appear as hyperechoic structures with a characteristic acoustic shadowing on the IVUS (figure 2).8 The IVUS can assess coronary artery calcification quantitatively (angle and length), semiquantitatively (absent or quadrant distribution), and qualitatively (depth of acoustic shadowing based on plaque and medial thickness).25 A study that compared IVUS to CA in 67 chronic total coronary occlusions (CTO) lesions found that IVUS was superior regarding the identification of calcium deposits (96% vs 61%).26 However, IVUS cannot evaluate microcalcifications (> 5 µm), but it can estimate the depth or thickness of calcium deposits.25

Figure 2. Coronary angiography (A) and intravascular ultrasound imaging (B) of ostial left anterior descending coronary artery showing severe concentric coronary calcification. Panels C, and D show the immediate outcomes after definitive stent implantation. CC, concentric calcification; GW, guidewire; SS, stent struts.

On the OCT, calcification appears as a heterogeneous structure with well-defined borders that can be used to offset some of the limitations of IVUS. Although the OCT has less depth penetration capabilities,25 its evaluation of the calcium thickness, area, and volume is more precise and reliable.27

The ICI analysis of calcium features can provide some insights for efficient planning to prevent stent underexpansion or malapposition.28,29 Therefore, calcium circumferences > 180º, thicknesses > 0.5 mm or lengths > 5 mm on the ICIs should involve adjunctive therapies to plaque modification.30 The OCT analysis of 31 patients from the Disrupt CAD study showed that calcium fractures were the leading mechanism of action of coronary lithotripsy and a tendency towards more adequate stent expansion was observed.31 Similar results were reported with rotational atherectomy where a study that evaluated 88 calcified lesions with both ICI modalities confirmed that OCT-guided rotational atherectomy was associated with better stent expansion (83% vs 72%; P = .0004), but with similar survival rates at the 1-year follow-up.32 Nevertheless, the IVUS may help while performing a PCI on the left main artery disease,33 where an early assessment can identify the optimal plaque modification technique to be used.34

Chronic total coronary occlusion lesions

The prevalence of CTO is 20% among patients with coronary artery disease. Performing a PCI on a CTO can improve the patients’ symptoms, workout abilities, and quality of life.35 The reported success rate for CTO procedures is estimated at 70% to 90%. With careful planning, better results can be achieved.36,37

IVUS provides an adequate and more efficient way to evaluate CTO features (cap ambiguity, lesion length, and calcification) allowing optimal re-entries into the true lumen with both antegrade and retrograde approaches.38 Studies that compared IVUS vs CA in PCIs performed on CTOs have yielded conflicting results regarding the rate of MACE (table 3).39-41 Furthermore, the IVUS has proven beneficial to predict restenosis in PCIs performed on CTOs where post-minimal luminal diameters of ≤ 2.4 mm and stent expansion rates of ≤ 70% were independent predictors of post-PCI restenosis at the mid-term follow-up, particularly in complex CTOs.42 A major limitation of IVUS guided PCIs performed on CTOs is the artifact generated by calcium rendering, which complicates the interpretation of images.38

Table 3. Invasive coronary angiography vs intracoronary imaging for percutaneous coronary interventions on chronic total coronary occlusions

Reference Type of study IVUS vs CA (n) Primary endpoint Study outcomes
Tian et al.39 Prospective RCT 130 vs 130 In-stent late lumen loss • Rate of stent restenosis (3.9% vs 13.7%; P = .021)
• Adverse event rate after 2 years (21.7% vs 25.2%; P = .641)
Hong et al.40 Retrospective 206 vs 328 Stent thrombosis • Similar rate of MACE in the matched cohort
• Lower stent thrombosis in IVUS-guided PCI (0% vs 3%; P = .015)
Kim et al.41 RCT 201 vs 201 Cardiac death • Less MACE (HR, 0.35; 95%CI, 0.13–0.97) and stent thrombosis (0% vs 1.5%; P = .11) in IVUS-guided PCI

CA, coronary angiography; IVUS, intravascular ultrasound; MACE, major adverse cardiovascular event; PCI, percutaneous coronary intervention; RCT, randomized controlled trial; OCT.

The main obstacle of the OCT in PCIs performed on CTOs is the need for contrast washout and the propagation of dissections due to the need for blood clearance, which is why it has been considered inadequate. However, this imaging modality could find its way into optimized PCIs performed on CTOs and follow-up monitorizations. A retrospective study reported a higher rate of stent malapposition and uncovered struts at 6-months after OCT examinations of patients with successful PCIs performed on CTOs.43 The ALSTER-OCT-CTO registry reported similar results after evaluating 111 lesions with OCT and saw a higher rate of malapposed and uncovered stent struts in CTOs vs non-CTO lesions at the 12-month follow-up.44

Coronary artery aneurysms

Coronary artery aneurysms are often clinically silent and can be identified in approximately 5% of all the patients undergoing CA. The most common causes are atherosclerosis in adults and Kawasaki disease in children. Coronary artery aneurysm is defined as a focal dilation of at least > 1.5 times the adjacent normal coronary artery while diffuse dilation is considered as coronary artery ectasia. Morphologically, when looked at from their maximum diameter, saccular and fusiform aneurysms can be seen with the former greater transverse rather than longitudinal diameter.45

The optimal ICI modality remains controversial, but historically IVUS has been the preferred approach for the evaluation and follow-up of coronary artery aneurysm in Kawasaki disease. The deeper penetration capabilities of IVUS allows us to assess the diameter of the vessel. Besides, it can accurately differentiate false from true coronary aneurysms by identifying a single-layered bulging. IVUS-guided preoperative planning is advised as aneurysms often go undersized with CA.45

Dionne et al. conducted an analysis of coronary artery aneurysms using OCT in a pediatric population with a past medical history of Kawasaki disease. The OCT proved to be safe, and similar findings (intimal hyperplasia, fibrosis, and media disruption) were observed in aneurysmal lesions compared to former histopathological studies. Nonetheless, these findings were also seen in non-aneurysmal coronary segments, which could drive the higher risk of ischemia in patients with a past medical history of Kawasaki disease.46

Left main coronary artery disease

The prevalence of LMCAD is 4% and, traditionally, coronary artery bypass graft has been the standard treatment with growing evidence to this date supporting PCI.47 Selecting the right imaging modality is important to determine accurately the clinical significance of LMCAD. CA remains the standard evaluation of choice, but it is subject to a high inter and intra-observer variability in the detection of intermediate lesions (30% to 70%).48 Consequently, intracoronary imaging can improve the assessment of LMCAD, and the long-term outcomes.

The importance of IVUS assessing the anatomy of LMCAD is evident given its more consistent tissue penetration capabilities that allows proper plaque evaluations. Former studies (table 4) described significant LMCAD with minimal lumen areas between 6 mm2 and 9 mm2 estimated using IVUS33,49 with values < 6 mm2 showing a good correlation with fractional flow reserve < 0.75.50 However, smaller areas have been reported in the Asian population.51 A multicenter prospective study that evaluated LMCAD with IVUS reported a similar rate of cardiac events after 2-years in patients undergoing revascularization with minimum lumen areas (MLA) < 6 mm2 (5.5%), as well as in those with MLAs ≥ 6 mm2 (2.3%) with revascularization deferral.33 Therefore, an angiographically ambiguous LMCAD with an IVUS-derived MLA > 6 mm2 can be considered non-ischemic whereas those with a MLA ≤ 4.5 mm2 could be deemed as ischemia-generating LMCAD. However, for those with a MLAs from 4.5 mm2 to 6 mm2, additional invasive or non-invasive assessment tools are required to rule out the presence of ongoing ischemia.52

Table 4. Summary of the studies that evaluated invasive coronary imaging for the assessment of left main coronary artery disease

Reference Type of study ICI use Follow-up time Outcomes
De la Torre Hernandez et al.33 Prospective multileft IVUS 2 years Defer PCI with MLA > 6 mm2 is safe
Fassa et al.49 Prospective IVUS 3 years Defer PCI with MLA ≥ 7.5 mm2 is safe
Jasti et al.50 Prospective IVUS 3 years MLA < 5.9 mm2 is well correlated with a FFR < 0.75
Park et al.51 Prospective IVUS NA FFR < 0.8 had a good correlation with MLA ≤ 4.5 mm2 among Asians

ICI, intracoronary imaging; IVUS, intravascular ultrasound; MLA, minimum lumen area; PCI, percutaneous coronary intervention.

Former studies have demonstrated that plaque burdens > 60% in non-LMCAD is a predictor of MACE and can be recognised when assessing the risk of future events after PCI.4 Through IVUS analysis, it was shown that the larger the plaque burden in the LMCAD, the greater the overall plaque burden in the coronary tree.53 However, in the PROSPECT study a greater plaque burden was not associated with a higher rate of MACE as opposed to the overall plaque burden (hazard ratio, 1.06; 95%CI, 1.01–1.11; P = .02).54 Therefore, the IVUS assessment of the LMCAD plaque burden can identify high-risk patients with coexisting non-LMCAD atherosclerotic disease.

The role of IVUS in LMCAD is not limited to diagnosis only (table 5).55-59 A meta-analysis that compared IVUS-guided vs CA-guided PCI in LMCAD found that the former was associated with less cardiovascular mortality (RR, 0.47; 95%CI, 0.33–0.66; P < .001), new target lesion revascularization (RR, 0.43; 95%CI, 0.25–0.73; P = .002), and stent thrombosis (RR, 0.28; 95%CI, 0.12–0.67; P = .004).60 Also, de la Torre Hernández et al. reported that IVUS-guided PCI was particularly useful in distal lesions with a lower event rate compared to non-IVUS guided PCI (hazard ratio, 0.54; 95%CI, 0.34–0.90).56 Other studies have proposed a role for IVUS in the optimization of LMCAD after stent deployment where minimum lumen areas were associated with stent underexpansion and could predict in-stent restenosis with different thresholds regarding the assessed segment (8 mm2 for the proximal left main coronary artery, 6 mm2 for the ostium of the left anterior descending coronary artery, and 5 mm2 for the ostium of the left circumflex artery).61

Table 5. Summary of the studies that compared IVUS-guided vs coronary angiography-guided percutaneous coronary interventions on left main coronary artery disease

Reference Endpoints Outcomes
Park et al.55 • Primary endpoint was all-cause mortality
• Secondary endpoints were MI, TVR, and the composite endpoint
• IVUS-guided PCI was associated with a lower rate of overall mortality (HR, 0.31; 95%CI, 0.19–0.51), and MI (HR, 0.470; 95%CI, 0.33-0.67).
• The risk of TVR (HR, 0.47; 95%CI, 0.33-0.67) did not decrease with IVUS guidance
De la Torre Hernandez et al.56 • Primary endpoint was MACE (cardiac death, MI, TLR)
• Secondary endpoints were all-cause mortality, cardiac death, infarction-free survival, TLR-free survival, and the rate of ST
• The 3-year rate of all-cause mortality was lower with IVUS-guided PCI (4.7% vs 16%; P = .048)
• Lower rate of ST with IVUS-guided PCI (0.6% vs 2.2%; P = .04)
• IVUS-guided PCI of LMCAD was associated with minor adverse events in distal lesions (HR, 0.34; 95%CI, 0.34-0.90), and in the overall population (HR, 0.70; 95%CI, 0.52-0.99)
Gao et al.57 • Primary endpoint was the 1-year rate of MACE (cardiac death, MI, TVR)
• Safety outcome was ST
• The 1-year rate of MACE in the IVUS-guided group was lower (14.8% vs 27.7%)
• Coronary angiography-guided PCI was associated with a higher rate of ST (2.7% vs 0.6%; P = .026)
Tan et al.58 • 2-year rate of MACE (death, MI or TLR) • Similar event rate regarding SR (3.28% vs 8.15%; P = .11), and ST (1.6% vs 3.2%; P = .568)
• The IVUS-guided PCI was associated with a lower rate of MACE (OR, 0.414; 95%CI, 0.129-0.867), and TLR (8.2% vs 19%; P = .045)
Andell et al.59 • Primary endpoint was a composite endpoint of all-cause mortality, SR, and ST)
• Secondary endpoints were all-cause mortality, SR, ST, and unexplained death within 30-days
• The IVUS group was associated with fewer composite endpoints (HR, 0.65; 95%CI, 0.50–0.84) and a lower all-cause mortality rate (HR, 0.62; 95%CI, 0.47–0.82)
• Not differences were seen in the rate of ST and SR

95%CI, 95% confidence interval; HR, hazard ratio; IVUS, intravascular ultrasound; LMCAD, left main coronary artery disease; MACE, major adverse cardiovascular event; MI, myocardial infarction; OR, odds ratio; PCI, percutaneous coronary intervention; SR, stent restenosis; ST, stent thrombosis; TLR, target lesion revascularization; TVR, target vessel revascularization.

On the contrary, the OCT has limited utility in the assessment of LMCAD given its average diameter (3 mm to 5 mm) and inability to evaluate aorto-ostial lesions where blood-free fields are difficult to achieve.48 A multicenter retrospective study (ROCK cohort II) recently reported a lower 1-year rate of target lesion failure in intravascular imaging guided vs angiographically guided distal PCIs on the LMCA (12.7% vs 21.2%; P = .039) with similar outcomes between the OCT and the IVUS (P = .26).62 However, future prospective data supporting OCT-guided PCI is expected to better define the optimal clinical management of patients with LMCAD (NCT04248777, NCT04391413, NCT03474432, NCT03820492, and NCT04531007).

Spontaneous coronary artery dissections

Spontaneous coronary artery dissection is a classically misdiagnosed life-threatening condition that can occur in otherwise healthy individuals. Coronary flow is compromised after the development of a false lumen through an “inside-out” or “outside-in” mechanism. The Yip-Saw coronary classification has revealed the limitations of coronary angiography. Diagnosis is particularly challenging with type 2 (diffuse smooth stenosis) and type 3 (mimic atherosclerotic stenosis) spontaneous coronary artery dissections.63,64

The benefits of implementing ICIs (table 6) for diagnostic purposes or even to guide coronary intervention in spontaneous coronary artery dissections are their higher resolution.65,66 IVUS has a deeper power of penetration to visualize the vessel wall and intramural hematoma, consequently, it is also recommended for proximal dissections8. It can also differentiate between true and false lumens once fused with color interpolation. However, the OCT is more sensitive regarding the identification of subtle signs such as an intimal tear (entry site to the false lumen), and Ribero et al. used it for establishing the mechanism behind coronary dissection.67

Table 6. Benefits of intravascular imaging modalities in spontaneous coronary artery dissection

Intramural hematoma (complete visualization of the vessel wall) Detail characterization of the intimal flap (intimal-medial disruption)
True and false lumen (with IVUS and ChromaFlo*) Connection between true-false lumen (entry tear)
Thrombosis of the false lumen Involvement of side branches and/or thrombus
Guidewire position Guidewire position

IVUS, intravascular ultrasound; OCT, optical computed tomography.

* Chromaflo Volcano (Philips, United States).

If the ICI is deemed necessary during the management of spontaneous coronary dissection, it is important to acknowledge that there is a risk of procedural complications (eg, dissections with contrast injection during the OCT, especially in type I spontaneous dissections or lead to vessel occlusion). A study of 28 patients with spontaneous coronary artery dissections found that intracoronary imaging assessment was associated with iatrogenic wire (3.5%) and guide catheter dissections (3.5%), but also with propagation with wiring (10.7%) or advancement of the OCT catheter (3.5%).68 Therefore, the benefit may be greater in cases of diagnostic uncertainty or with complex dissections requiring PCI.

Heart transplant vasculopathy

The clinical presentation of cardiac allograft vasculopathy is often silent. Still, it is characterized by aggressive and concentric diffuse fibromuscular dysplasia. The International Society for Heart and Lung Transplantation classifies allograft vasculopathy into 4 categories based on graft function and angiographic findings having CAV2 and CAV3 the worst prognosis of all.69 CAV is considered the gold standard technique for routine screening and definitive diagnosis.

Heart transplant patients may present with an intimal thickening identifiable through IVUS only. Former studies have reported that an intimal thickening > 0.5 mm from baseline is associated with a higher rate of adverse events within the first year after the heart transplant.70,71 Consistent with these findings, volumetric studies with IVUS have shown that the combination of intimal thickening plus negative remodelling of the proximal left anterior descending coronary artery were associated with acute rejection and major adverse events within the first year.72 However, the OCT can identify early stages of intimal thickening in the form of intimal hyperplasia (thickness > 100 µm), and improve the clinical outcomes.73

Post-stent findings

Both imaging modalities have been used to identify stent underexpansion, incomplete apposition, and edge dissection as potential causal mechanisms of stent failure.

In this regard, minimal stent area (MSA) is associated with both restenosis and stent thrombosis. IVUS studies reported MSAs between 5.3 mm2 and 5.7 mm2 with smaller areas identified in patients with definitive stent restenosis at the short-term follow-up after stent implantation.74,75 Similarly, 2 studies reported that MSAs < 5 mm2 as seen on the OCT were associated with a higher rate of target lesion revascularization and stent thrombosis with drug-eluting stents.76,77 On the contrary, stent patency assessed through the OCT suggested that values > 4.5 mm2 had a lower rate of MACE,76 but higher cut-off values for proximal (> 8 mm2) and distal (> 7 mm2) LMCA with IVUS assessment. Therefore, clinical guidelines recommend a post-PCI MSA/mean reference lumen of > 80%.

A series of OCT registries observed that a common leading mechanism responsible for early (1 to 30 days), late (1 to < 12 months), and very late (> 1 year) thrombus formation is the malapposition (axial distance > 0.4 mm with a longitudinal extension > 1 mm) of stented segments.78-80 Consistent with this, stent edge dissection is also associated with adverse events as seen on the CLI-OPCI II study, where distal stent edge dissections > 200 µm had a higher rate of MACE.76


The development of ICI techniques has resulted in significant clinical improvements, but they are not free from procedural complications (figure 3).

Figure 3. Post-stent findings with optical coherence tomography: A: stent malapposition from the 16 o’clock to the 19 o’clock position; B and D: edge dissection with flap (white asterisk) distal to an implanted drug-eluting stent; C: stent restenosis (white arrow) due to concentric neointimal proliferation; the stent struts are visible under the homogenous bright layer. ED, edge dissection; GW, guidewire; ISR, in-stent restenosis; MALD, malapposed distance; SA, strut apposition; SMA, strut malapposition; SS, stent struts.

Safety trials on IVUS have reported an estimated rate of complications between 1% to 3%, mostly associated with the size of the catheter. The setback of CA is the use of contrast materials to enhance image quality with the inherent risk of contrast-induced nephropathy.81 On this regard, a small retrospective study of 37 patients with advanced kidney disease evaluated the safety of IVUS-guided zero contrast PCI without a higher rate of renal replacement therapy or MACE being reported.82 Similar findings were described in a prospective and multicenter study,83 and a randomized control trial.84 Safety and feasibility have also been assessed on the OCT without a higher rate of MACE,85 procedural complications or acute kidney injury being reported.86 Additionally, data from 2 prospective studies suggests that contrast-less OCT would be a feasible imaging modality.87,88

In former studies that compared ICI modalities (table 7), similar complication rates were reported.89-91 Van der Sijde et al. used a prospective study to compare the procedural complications of both ICIs and did not observe a higher event rate during image acquisition. Also, they did not identify any potential risk factors regarding major adverse events suggesting that both the safety and feasibility of ICIs are greater than expected and unrelated to the operator’s experience.92

Table 7. Summary of studies comparing IVUS vs OCT and/or CA for PCI guidance

Reference Type of study ICI modality Outcomes
Ali et al.89 Multileft RCT OCT vs IVUS vs CA No differences in procedural MACEa were reported between OCT (3%) and IVUS (1%; P = .37) and CA (1%; P = .37)
Similar rate of procedural complication
Habara et al.90 Prospective RCT OCT vs IVUS Similar rate of procedural time (40 ± 16.4 min vs 47 ± 17.6 min; P = .09), and fluoroscopy time (20.4 ± 8.4 min vs 24.8 ± 10.4 min; P = .05)
Similar rate of complications, no deaths reported (P > .99)
Kubo et al.91 Prospective multileft RCT OCT vs IVUS Similar rates of cardiac death (0% vs 0.2%; P = .99) and MACEb (2.9% vs 3.5%; P = .81)
No contrast-induced nephropathy reported with a similar rate of complications between the groups
Van der Sijde et al.92 Single-left
OCT vs IVUS Similar rate of procedural cardiac events (< 1%)
No predictors of adverse events were identified

CA, coronary angiography; ICI, intracoronary imaging; IVUS, intravascular ultrasound; MACE, major adverse cardiovascular event; OCT, optical computed tomography; RCT, randomized controlled trial.

a Defined as procedural complications (angiographic dissection, perforation, thrombus, or acute closure), and active procedures (balloon inflations, additional stent implantations or pericardiocentesis).

b Defined as a composite of cardiac death, myocardial infarction or ischemia-driven target lesion revascularization.


Beyond the limitations of coronary angiography, coronary assessment remains complex given the different forms of presentation. Therefore, the ideal imaging modality would be one that is easy to use, interpret, and safe. Intracoronary imaging guidance is widely recognized for diagnosis, PCI planning, and to guide post-PCI treatment. However, there is still room for improvement, and future randomized studies will contribute to the wider adoption of these imaging modalities in all cath labs.


None whatsoever.


Á. Aparisi drafted the original manuscript. Á. Aparisi, H. Cubero-Gallego, and H. Tizón-Marcos were involved in the process of critical revision of the manuscript regarding significant intellectual content, and eventually wrote the final version. All authors read and gave their publication consent for this version of the manuscript.


None reported.


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* Corresponding author:

E-mail address: htizon@psmar.cat (H. Tizón-Marcos).


Heart failure (HF) is the leading cause of hospitalization in the Western world. Despite improvements in diagnostic tools and therapies, a substantial number of patients with HF still remain highly symptomatic, with a poor quality of life. Most of these patients are ineligible for heart transplantation or left ventricular assist device placement, which underscores an unmet clinical need in this population. Novel device-based HF therapies represent therapeutic options for these patients to improve their symptoms and quality of life. First-in-man studies showed promising results in terms of feasibility, and device performances. However, there is still scarce data regarding efficacy. In this review, we focus on the pathophysiological rationale, emerging data, concerns, and future perspective behind the 3 most studied type of device-based HF therapy: interatrial shunt devices, designed to decompress the left atrium and prevent pulmonary edema; ventriculoplasty devices, designed to physically restore the left ventricle in patients with maladaptive left ventricular remodeling; and cardiorenal flow modulator devices, designed to improve diuresis and renal function in acute decompensated heart failure with cardiorenal syndrome.

Keywords: Heart failure. Novel devices. Interventional cardiology.


La insuficiencia cardiaca (IC) es la principal causa de hospitalización en los países desarrollados. A pesar de las mejoras en el diagnóstico y las terapias, una proporción importante de pacientes con IC aún persisten muy sintomáticos o con pobre calidad de vida. La mayoría de estos pacientes, además, no son candidatos a trasplante cardiaco ni a asistencia ventricular de destino. Así pues, existe una necesidad clínica no cubierta de tratar a este creciente subgrupo de pacientes. Los nuevos dispositivos percutáneos para IC son una opción de tratamiento para mejorar los síntomas y la calidad de vida de estos pacientes. Los primeros estudios en humanos con estos dispositivos han mostrado unos resultados prometedores en términos de factibilidad, seguridad e integridad de los dispositivos. No obstante, todavía hay pocos datos sobre su eficacia. En esta revisión nos centramos en describir las características, las ventajas y los inconvenientes, así como las evidencias, de los 3 tipos principales de dispositivos percutáneos para la IC, con especial énfasis en la base fisiopatológica subyacente que justifica su diseño: los dispositivos de derivación interauriculares, que pretenden descomprimir la presión de la aurícula izquierda y así evitar el edema pulmonar; los dispositivos de ventriculoplastia, que restauran físicamente el ventrículo izquierdo en situaciones de mal remodelado ventricular; y los dispositivos de modulación del flujo cardiorrenal, diseñados para mejorar la diuresis en situación de IC aguda descompensada con síndrome cardiorrenal asociado.

Palabras clave: Insuficiencia cardiaca. Nuevas terapias. Cardiología intervencionista.

Abbreviations ADHF: acute decompensated heart failure. GDMT: guideline-directed medical therapies. HF: heart failure. HFrEF: heart failure with reduced ejection fraction. IASD: interatrial shunt device. LV: left ventricle. RV: right ventricle.


Heart failure (HF) is the leading cause of hospitalization in the Western world, and a major issue for public health. The estimated prevalence of HF is between 1% and 2% in the adult population in developed countries, and up to 10% among patients aged > 70 years.1 Despite improvements in diagnostic tools and guideline-directed medical therapies (GDMT) such as continuous monitoring of pulmonary artery pressures, sacubitril, and selective sodium–glu- cose cotransporter 2 inhibitors, a significant proportion of patients with HF remain symptomatic and with a poor quality of life.2-4 According to the latest European data, the annual mortality and re-hospitalization rates in patients with HF are between 7%-17%, and 34%-44% respectively.4 Most of these individuals are ineligible for heart transplantation or left ventricular assist device placement, which underscores an unmet clinical need in this ever growing population. Consequently, novel applications of minimally invasive, device-based therapies are being developed to bridge this treatment gap, that is now starting to fall into an emerging sub-specialty called «interventional heart failure». Novel device-based HF therapies may represent an option to improve the quality of life and reduce the rates of hospitalization or even mortality of these patients who are GDMT-optimized, yet with residual morbidity and suboptimal quality of life.

This article will focus on the pathophysiological rationale and emerging data and concerns behind some of these device-based HF therapies that have been designed to target a range of mechanisms involved in the HF syndrome.


An early sign of left ventricular (LV) failure (involving both preserved or reduced ejection fraction) is an increased LV end-diastolic pressure, retrogradely transmitted to the left atrium and pulmonary capillaries causing dyspnea and ultimately pulmonary edema if left untreated.5 Interatrial shunt devices (IASD) create a permanent interatrial communication using a conventional percutaneous transseptal approach. It is intended to dynamically decompress left atrial pressure, and thus, attenuate or even reverse the underlying mechanism of pulmonary edema.6 However, left-to-right interatrial shunt may increase right ventricular (RV) preload and eventually RV dilatation. Prior studies suggest that the size of the shunt plays a key role in the final outcomes. Indeed, the ideal size of the shunt should allow the reduction of left atrial pressure without hampering right heart function: too large IASDs may increase the Qp/Qs ratio enough to cause RV failure while too small IASDs may have negligible hemodynamic and clinical effects. Data from first-in-man studies indicate that devices < 10 mm are unlikely to cause hemodynamically significant shunting (ie, Qp/Qs ratio > 1.5) or RV size/functional compromise.7 The 2 shunt devices most studied to date are the 5 mm- (V-Wave device, V-Wave Ltd., Israel) and 8 mm-long (Interatrial Shunt Device, Corvia Medical, United States) in diameter apertures (figura 1A, figura 1B and table 1).8 Another concern is related to patients with stiff or fibrotic atria or RV. In this scenario the right atrium or RV may not be able to accept an increased preload. For all these reasons, patients with restrictive cardiomyopathy, pulmonary hypertension (pulmonary vascular resistance > 4 Wood units) or RV dysfunction have been excluded from shunt studies. Finally, paradoxically, strokes due to transient flow reversal are another potential concern when using this technology.

Figure 1. Interventional heart failure therapy devices. A: V-Wave (V-Wave Ltd., Israel) is an interatrial shunt device with an hourglass-shaped self-expandable nitinol frame and expanded PTFE skirt with 5 mm central hole. B: Interatrial Shunt Device (Corvia Medical, United States) provides 8 mm of central hole. C: AccuCinch ventricular restoration system (Ancora Heart, United States) is a fully percutaneous left ventriculoplasty device. D: Revivent TC System (BioVentrix Inc., United States) is a left ventriculoplasty device that uses micro-anchors to exclude a scar via hybrid approach (jugular plus mini lateral thoracotomy). E: Doraya catheter (Revamp Medical, Israel) reduces both the venous renal hypertension and preload to improve diuresis in acute decompensated heart failure (ADHF) with cardiorenal syndrome (CRS). F: Aortix (Procyrion Inc., United States) device is a pump that improves the renal arterial perfusion pressure and reduces the left ventricular afterload. Aortix is intended to improve diuresis in ADHF with CRS.

Table 1. Device mechanism, features and, evidence of interventional heart failure devices

Device Device mechanism & features Trial Study design Main inclusion criteria N Main results
V-Wave – Interatrial shunt (transseptal approach).
– Fully percutaneous (via femoral vein using a 12-Fr delivery system).
– Hourglass-shaped device on a nitinol frame with an expanded PTFE skirt.
– Lumen diameter: 5 mm.
– Second generation has no unidirectional valve to ensure left-to-right shunt
VW-SP-1 + Canadian cohort8 Multicenter, single-arm, open-label, phase I trial with a 12-month follow-up – NYHA class III-IV; ≥ 1 HF hospitalization within the last year or ↑ BNP 38 (30 with HFrEF) – 1-year rate of MACE: 2.6% (1 tamponade)
– Significant improvements in NYHA class, QoL, KCCQ
– Significant increase in the Qp/Qs ratio
Multicenter, sham-controlled, blinded RCT with a 1:1 allocation ratio, and a 1-to-2-year follow-up – NYHA class II-IV; ≥ 1 HF hospitalization within the last year or ↑ BNP PCWP > RAP; PVR < 4 WU; transseptal eilgible 500 (ongoing) Enrolling (estimated completion by 2022)
– Endpoints: device MDAE, MACE, NYHA, KCCQ, and 6MWT
Interatrial Shunt Device – Interatrial shunt (transseptal approach)
– Fully percutaneous (femoral vein)
– Nitinol, self-expanding metal cage with a double-disc design and an opening (barrel) in the center
– Central hole of 8 mm
Multicenter, open-label, single-arm with a 6-month follow-up – NYHA class II-IV; LVEF > 40%; PCWP ≥ 15 mmHg (or 25 mmHg exercise) 64 – No MACE; 52% had a reduction in resting PCWP; 54% had a reduction in PCWP during exertion; improvement in NYHA class; QoL, and 6MWT
Multicenter, double-blind, sham-controlled RCT with a 1:1 allocation ratio, and a 1-year follow-up – NYHA class III-IV; LVEF > 40%; Exercise PCWP ≥ 25 mmHg; PCWP-RAP ≥ 5 mmHg; prior HF hospitalization or ↑BNP 44 – Reduction in PCWP on exercise; similar rate of MACCE, and no strokes in either one of the 2 arms.
– Trends of reduction of HF-related hospitalizations; improvement in QoL, and RV size in the device arm
Revivent TC System – Ventriculoplasty
– Hybrid (jugular vein + mini lateral thoracotomy)
– Anchors and external locking on the LV epicardial surface
Multicenter prospective RCT with a 6-month follow-up (2:1 allocation ratio; device vs guideline-directed medical therapy) – HF symptoms with previous myocardial infarctio, increased LV systolic volume, and contiguous scar located in the anterior/ apical LV 180 (ongoing) Enrolling (estimated completion by 2022).
– Endpoints: 6MWT distance at 6 months; QoL at 6 months; change in NYHA class at 6 months; LVESVI at 6 months; LVEF at 6 months
AccuCinch Ventricular Restoration System – Ventriculoplasty
– Fully percutaneous; femoral artery access, retrograde aortic approach; initially designed for mitral regurgitation
– Cinching anchors attached to the mitral subvalvular apparatus
Multicenter, open-label, RCT with a 5-year follow-up. – NYHA class II-IV; LVEF, 20% to 40%; and LVEDD > 55 mm; 6MWT distance, 100 m to 450 m 400 (ongoing) Enrolling (estimated completion by 2025)
– Endpoints: MAEs at 6 months, and 1 year; changes in the KCCQ score; change in the 6MWT; composite of all-cause mortality, LVAD implant or heart transplantation, HF hospitalizations, and changes in the KCCQ score
Papillary muscle sling – Ventriculoplasty
– Femoral artery access, retrograde aortic approach
– 4 mm PFTE graft implanted around the base of the papillary muscles and then tightened
NCT04475315 Single-center, open-label RCT (1:1 allocation ratio; CABG vs CABG + sling) with a 5-year follow-up – NYHA class II-IV; LVEDD ≥ 55; LVEF 20% to 40%; FMR ≤ 2+; end-systolic interpapillary muscle distance
≥ 20 mm; ischemic or nonischemic cardiomyopathy
40 (ongoing) Enrolling (estimated completion by 2026)
– Endpoints: changes of LVEF and LV volume, mortality, MACE, functional mitral regurgitation severity, change in QoL and the 6MWT, all-cause readmission, HF readmission, and in the rate of mitral leaflet tenting area
Doraya catheter – Venous renal flow modulator via femoral vein (12-Fr delivery system)
– Decreased renal hypertension and RV preload
NCT03234647 Multicenter, first-in-man, single-group study of feasibility, and safety – ADHF with poor diuretic response 9 Enrolling ended back in May 2021.
– Device-related or procedural serious adverse events at 60 days
Aortix – Arterial renal flow modulator via femoral artery (18-Fr delivery system)
– Pump that increases aortic flow (up to 5 L/min), and renal perfusion pressure, and reduces the LV afterload
NCT04145635 Multicenter, prospective non-RCT of feasibility and safety – ADHF with HFrEF or HFpEF
– Worsening renal function after 48 hours of IV diuretics (increase of 0.3 mg/dL)
– Persistent congestion (PCWP ≥ 20 or central venous pressure ≥ 12mmHg)
60 (ongoing) Enrolling (estimated completion by 2022)
– Endpoints: 30-day serious adverse events, serious procedural adverse events, device performance, 7-day decrease of central venous pressure or PCWP > 20%, changes in urine output, and lower BNP levels by 20%

6MWT, 6-minute walk test; ADHF, acute decompensated heart failure; BNP, brain natriuretic peptide; CABG, coronary artery bypass graft; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; HFpEF, heart failure with preserved ejection fraction; IV, intravenous; KCCQ, Kansas City Cardiomyopathy Questionnaire; LV, left ventricle; LVAD, left ventricular assist device; LVEDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction; LVESVI, left ventricular end-systolic volume index; MACE, major adverse cardiovascular event; MACCE, major adverse cardiovascular and cerebrovascular event; MAE, major adverse event; MDAE, medical device adverse event; NYHA, New York Heart Association; PCWP, pulmonary capillary wedge pressure; PVP, pulmonary vascular resistance; QoL, quality of life; RAP, right atrial pressure; RCT, randomized clinical trial; RV, right ventricle.

The first-in-man experience with both the V-wave and the Corvia Medical devices showed significant improvements in quality of life, HF symptom relief, and exercise capacity.6,8-9 There are currently several ongoing studies, and randomized clinical trials assessing IASD in patients with symptomatic HF despite GDMT including both HF with reduced or preserved LV function patients (table 1, REDUCE LAP-HFREF trial [NCT03093961], REDUCE LAP-HF trial II [NCT03088033], and REDUCE LAP-HF IV [NCT04632160]).


The LV has a unique architecture with 3 different myofiber orientations and an elongated ellipsoid shape that are essential for its optimal function. Different pathological states cause molecular and cellular changes that alter the obliquity of the myofibers, which become more horizontal, and macroscopically result in chamber dilatation and increased sphericity. This early adaptive response is ultimately detrimental and self-propagating, resulting in a loss of ventricular function (maladaptive remodeling). Maladaptive LV remodeling is clearly associated with poor prognosis.10

Ventriculoplasty refers to a physical intervention aimed to anatomically modify the LV geometry. The rationale is based on Laplace’s Law, according to which wall tension and LV wall stress are decreased by reductions in the LV radius, thus reversing or attenuating maladaptive LV remodeling. Compared to the ejection fraction, LV volume reduction is likely to be equally important in improving symptoms and possibly clinical outcomes. Prior surgical attempts of this concept showed disappointing results due to protocol deviations, and poor patient selection, thus contributing to less than anticipated LV volume reductions compared to the control arm. However, a post-hoc analysis demonstrated promising results (significant and sustained mortality reductions out to 6 years) in patients with an achieved LV end-systolic volume index < 70 mL/m2 with strong trends in survival advantage in patients who achieved a 30% threshold in LV end-systolic volume index reduction.11 Despite the controversial results of surgical LV reconstruction, there is considerable interest in percutaneous reverse LV remodeling, specifically in patients with HF with reduced ejection fraction (HFrEF). Several methods have been developed to perform percutaneous left ventriculoplasties. However, we will be focusing on the 3 methods that showed promising results in early feasibility studies: the Revivent TC system (BioVentrix Inc., United States), the AccuCinch (Ancora Heart, United States), and the papillary muscle sling.

The BioVentrix Revivent TC system is a hybrid transcatheter procedure via mini lateral thoracotomy and transcatheter jugular access. The system is designed to exclude an aneurysm or scar located in the anterior or apical LV wall. A hinged anchor is deployed inside the RV side of the distal interventricular septum (via jugular access) and 1 external locking anchor on the LV epicardial surface (via minithoracotomy). A tether is used to draw the 2 anchors towards each other until enough contact between the 2 opposing walls has been achieved. This action is repeated along the long axis of the LV, resulting in the exclusion of the dysfunctional scar tissue from a healthy and functional myocardium (figura 1C). Data from a study of 86 patients demonstrated improvements in the LV ejection fraction, LV volumes, quality of life, and functional status.12 Currently, there are 2 pivotal trials assessing this therapy (the REVIVE-HF [NCT03845127], and the ALIVE [NCT02931240]) (table 1).

The AccuCinch ventricular restoration system consists of a predesigned tracking catheter that, via retrograde aortic access, is positioned to encircle the basal aspect of the LV, which is used to position a band anchored to the basal LV myocardium. Tension is applied to a cable reducing the basal wall diameters and the LV volumes13 (figura 1D). Although this device was initially designed to treat functional mitral regurgitation, the current focus remains on patients with HFrEF. There is currently an ongoing pivotal randomized clinical trial assessing this device in individuals with HFrEF vs GDMT (table 1, CORCINCH-HF [NCT04331769]).

The papillary muscle sling procedure, based on an existing surgical sling procedure, is aimed at reducing the lateral interpapillary muscle separation distance. A sling is used to draw together the LV via retrograde aortic access. Currently, there is 1 clinical trial assessing this technique in a surgical cohort (table 1, NCT04475315).


Acute decompensated HF (ADHF) in patients with prior renal injury and/or cardiorenal syndrome is an extremely challenging scenario for medical management. The pathophysiology of cardiorenal syndrome is complex, dynamic, and multifactorial, including hemodynamic and neurohumoral axis alterations.14 Data from previous studies suggest that the difference between renal arterial driving pressure and venous outflow pressures must remain sufficiently large for the proper renal blood flow and glomerular filtration. Maintenance of this homeostatic mechanism is especially important in patients with preexisting renal injuries. In patients with ADHF and cardiorenal syndrome, both pre-renal perfusion reduction, and renal venous hypertension are present. Renal venous hypertension increases renal resistance, which in turn impairs intrarenal blood flow. The decrease in renal perfusion is aggravated by the preglomerular vasoconstriction caused by the neurohumoral activation of the renin-angiotensin-aldosterone axis, which results in increased proximal tubular sodium and water reabsorption to maintain an effective plasma volume. This results in oliguria, worsening congestion symptoms, and diuretic resistance. The relationship between diuretic resistance and poor outcomes in this scenario is well established.14

There are 2 main types of devices designed to interrupt the vicious circle of cardiorenal syndrome in ADHF: those aimed at reducing renal venous hypertension such as the Doraya catheter (Revamp Medical, Israel); and those aimed at increasing arterial renal perfusion pressure such as the Aortix (Procyrion Inc., United States) and the Second Heart Assist (Second Heart LLC, United States) devices.

The Doraya catheter is a self-expanding flexible nitinol frame covered in its distal portion to restrict blood flow. It is placed in the inferior vena cava below the renal vein via femoral vein access using a 12-Fr delivery system. It serves as a temporary flow regulator for up to 24 hours. Doraya causes a temporal decrease in central venous pressure at the renal vein level, thus reducing cardiac preload, and contributing to LV unloading15 (figura 1E). A first-in-man clinical study to assess the safety, feasibility, and hemodynamic effects of this device in patients with ADHF, congestion, and an inadequate response to diuretics completed enrollment back in May 2021 (table 1, NCT03234647).

Aortix is a percutaneous axial pump positioned in the suprarenal descending aorta via transfemoral approach using an 18-Fr delivery system. This device increases aortic flow, decreases afterload, and can provide up to 5 L/min (figura 1F). A study performed in the percutaneous coronary intervention setting demonstrated a 10-fold increase in urine output.16 There is an ongoing study aimed at evaluating the feasibility, safety, and efficacy profile of Aortix in patients with ADHF (HF with preserved ejection fraction, and HRrEF), and cardiorenal syndrome (table 1, NCT04145635).

Despite improvements made in the management of HF, a substantial proportion of patients still remain severely symptomatic, and with a poor quality of life. Interventional HF is a promising new field within interventional cardiology to provide a percutaneous device-based therapeutic response to these patients. Interatrial shunts, percutaneous ventriculoplasties, and cardiorenal flow modulators are some of the most remarkable devices in this emerging field.


None whatsoever.


The authors have contributed equally in all the writing/design phases of this manuscript.


None declared.


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* Corresponding author: Interventional Cardiology Section, Department of Cardiovascular Medicine, 9500 Euclid Ave (J2-3), Cleveland Clinic, Cleveland, OH 44195, United States.

E-mail address: purir@ccf.org (R. Puri).

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