Debate: MitraClip. The heart failure expert perspective

QUESTION: What are the implications of aortic valve calcification on the outcomes of transcatheter aortic valve implantation (TAVI)?

ANSWER: Aortic valve calcification has, undoubtedly, been a major influence on TAVI outcomes and the evolving design of heart valves. Severe calcification has been associated with an increased likelihood of complications or poor outcomes, particularly in terms of residual paravalvular leak, need for postoperative pacemaker implantation, or aortic annular rupture, among others.1 Several generations of TAVI prostheses have mainly evolved with the aim of reducing paravalvular leak,2 through the use of skirts and coverings that facilitate sealing by adapting to the irregularities caused by annular and outflow tract calcifications. The goal is to balance sealing capacity with the optimal radial force needed, preventing excessive force that could cause conduction disturbances or, more critically, annular rupture. This emphasizes the critical role of procedural planning, which must account for the extent of calcification in all affected tissues. This meticulous planning, combined with experienced judgment and a deep understanding of the behaviour of each prosthesis is crucial for selecting the correct valve size.

Q.: What morphological and quantitative aspects of valvular calcification do you assess at your center?

A.: In addition to the usual annular measurement, in patients with severe calcification it is important to systematically identify the distribution and extent of calcium:

• – Sinotubular junction: at this level, it is crucial, especially when using a balloon-expandable valve, to determine whether calcification may compromise balloon inflation and, in the worst-case scenario, trigger balloon rupture, resulting in incomplete valve deployment with the risk of embolization, and the possibility of barotrauma-related dissection or aortic rupture in extreme cases. Therefore, it’s important to measure the minimum diameter between the most prominent calcium spicules and the contralateral border to confirm that the size of the balloon inflated with the necessary volume to deploy the selected prosthesis is not larger than that diameter.
• – Coronary ostium: Calcified plaques in the aortic wall near the coronary artery origins can increase the risk of coronary occlusion if displaced during valve deployment. Identifying this risk is crucial for implementing appropriate coronary protection strategies.
• – Sinuses of Valsalva and leaflets: first, it must be determined whether 3 sinuses are present or if we are facing a bicuspid valve, which has typical calcification patterns. The presence of calcified commissural fusions may require balloon predilatation to ensure passage through the valvular plane with the prosthesis and predict the leaflet behavior relative to the coronary arteries. The calcium will redistribute but will not disappear, so if calcium nodules are present on the leaflets occupying the sinus floor, we must consider the depth of the sinuses, and the association between leaflet length and coronary ostium height. If these sizes are suboptimal, the calcified leaflet may evert and occlude the coronary artery detaching from its base, or perforating the aortic wall if space is extremely limited.
• – Aortic annulus: evaluating calcium distribution at this level is crucial, as this is where the prosthesis will exert its greatest radial force. Symmetrical distribution throughout the annular circumference (360°) is rare but undoubtedly one of the most complex scenarios to deal with. In this case, one must assess the depth of calcium into the outflow tract and consider higher or lower implantation depths if it achieves sealing in a less calcified area. If not, an additional measurement beyond the annulus in the outflow tract should be taken to determine if the annular/tract anatomy is straight tubular, flared, or tapered. This information can help us oversize or undersize the prosthesis. However, typically, calcium is more focally distributed, with “teeth” extending toward the outflow tract, especially from the left coronary sinus toward the mitral-aortic continuity. A critical point is often a thinning area where the annulus transitions to the outflow tract, which is precisely where the distal end of the valve is usually positioned. This distribution presents one of the highest risks of rupture, specifically at the calcium thinning site, due to a physical principle: denser calcium regions are more resistant to deformation, so if density is not uniform, energy tends to be released where resistance is at its lowest point, potentially causing rupture. Therefore, planning should account for transitions between highly and minimally calcified zones when making decisions on implantation depth. Heterogeneous calcific density likely increases the risk of complications.

Q.: How does the degree of calcification affect valve type selection?

A: Perhaps the operator’s experience with the chosen valve model is the most influential factor in minimizing complications in heavily calcified scenarios, as operators know the limits of the technology they’re using. However, assuming comparable experience, in my opinion, balloon-expandable valves offer an advantage in expansion capacity and deployment control, allowing for more precise positioning. The combination of a low-recoil alloy and a balloon that inflates progressively and uniformly provides the necessary radial force to overcome calcium resistance while enabling control to stop inflation if high resistance or asymmetry is detected, preventing complications. While the idea that the prosthesis adapts to annular morphology is attractive, despite many self-expanding valves having supra-annular valve mechanisms, the risk of underexpansion is likely high3 requiring aggressive pre- and post-dilatations to create space and prevent recoil. Balloon-expandable technology allows for better sphericity indices in a more controlled and progressive way when appropriate proper implantation technique is used.

Q.: And how does the degree of calcification affect valve sizing?

A: Generally, in these scenarios, the goal with a balloon-expandable valve should be to avoid exceeding 5% oversizing, achieved by adjusting the inflation volume based on the valve nominal size, which usually leads to choosing smaller sizes or inflation volumes than usual for the same annular size in the absence of calcium. Caution in size and inflation volume selection is a great ally in avoiding complications. You can always opt for more aggressive inflations later if necessary and if the initial calcium modification allows. Of note, these valves will gradually expand and modify calcium, so controlled inflation is arguably more important than the final volume used.

Q.: Does the procedure differ based on valve calcification?

A: Technically, several peculiarities should be considered in the presence of a heavily calcified valve:

• – Predilatation: in standard cases, direct implantation of the balloon-expandable valve without predilatation is typical. In high calcium scenarios, predilatation offers several advantages, such as assessing calcium behavior in the sinuses of Valsalva and its relationship with coronary arteries, especially with simultaneous contrast injection. If calcification affects the sinotubular junction, predilatation may help determine the actual risk of balloon rupture during valve release. Most importantly, in cases of calcified commissural fusion, effective predilatation facilitates passage through the valve plane without the need fr aggressive push maneuvers. However, balloon predilatation in such situations may theoretically increase the risk of embolizing calcium debris during inflation, making it a potential indication for cerebral protection devices. Non-homogeneous calcium distribution can cause the asymmetric expansion of the prosthesis, thus shortening more in areas with less or no calcium compared with denser regions. While this does not compromise the functionality of valve, it should be considered when planning very high implantation depths. With balloon-expandable valves, residual leak is usually absent in standard implantation. In cases of high-grade calcification, we must be cautious in pursuing this goal, as it may involve forcing expansion that endangers the patient, especially during postdilatation. Remember that in reducing paravalvular (not central) regurgitation, skirt design is highly effective, and its effect may take a few minutes. Therefore, before aggressive postdilatation, it is advisable to allow time for the distal skirts to take effect.
• – Postdilatation: the first postdilatation should be performed with the same volume as deployment inflation, keeping it fully inflated for, at least, 5 seconds before increasing the volume in subsequent inflations.

If planning reveals a real risk of coronary artery occlusion, protection techniques should be considered.

Q.: What are the advantages of self-expanding prostheses in the most severely calcified valves?

A.: In addition to previously discussed aspects, of note, the ability of balloon-expandable technology to yield excellent results in reducing paravalvular leak,4,5 which is one of the main causes of poor outcomes in calcified prostheses. Moreover, with good planning and proper sizing, highly precise implantations can be achieved, with direct and progressive calcium modification, minimal recoil risk, and less need for postdilatation. The ability to achieve more precise implantations reduces the need for pacemaker implantation as well. Additionally, excellent outcomes have been demonstrated in patients with bicuspid valves, even though these often present with high calcium loads and varied distributions. In conclusion, balloon-expandable technology offers potential advantages in these patients due to its radial strength, control, implantation precision, and lower rates of paravalvular leak and need for pacemaker implantation,6 provided that proper planning goes beyond simple annular sizing, including thorough assessment of calcium distribution and correct size selection, and, above all, adequate knowledge of the prosthesis and the experience needed to handle this complex scenario. Undoubtedly, scientific evidence is needed to determine, beyond opinions, what technology is better, an answer that must come from ongoing clinical trials comparing the new TAVI valves under specific clinical conditions, such as extensive valve calcification.

FUNDING

None declared.

STATEMENT ON THE USE OF ARTIFICIAL INTELLIGENCE

No artificial intelligence was used.

CONFLICTS OF INTEREST

Cristóbal A. Urbano-Carrillo is a proctor for Edwards Lifesciences and participates in advisory groups for Medtronic Spain.

REFERENCES

QUESTION: Clinical practice guidelines have raised the recommendation level for the use of intravascular imaging during percutaneous revascularization procedures for complex lesions to class I. Can you briefly explain the basis for this change?

ANSWER: The clinical benefit of intracoronary imaging-guided revascularization has been evaluated in various clinical studies, including observational registries, randomized clinical trials, and meta-analyses.1,2 However, the publication of 3 large randomized clinical trials has formed the basis for the update of clinical practice guidelines. Firstly, the RENOVATE-COMPLEX-PCI study3 assessed the clinical impact of an intracoronary imaging-guided revascularization strategy (intravascular ultrasound [IVUS] or optical coherence tomography [OCT]) compared with angiography in complex coronary lesions. One of the strengths of this study is its inclusion criteria, which emcompass a heterogeneous yet well-represented group of complex lesions beyond the left main coronary artery, such as true bifurcations, chronic total occlusion, long coronary artery disease, multivessel angioplasty, implantation of multiple stents (more than 3), severe calcification, in-stent restenosis, and ostial lesions. intracoronary imaging-guided revascularization—74% with IVUS and 26% with OCT—was associated with a 36% reduction in the composite endpoint of death, myocardial infarction, and need for revascularization. Similarly, the OCCUPI study4 demonstrated the superiority of OCT vs angiography as a guide in complex procedures, with a 38% reduction in the rate of major adverse cardiovascular events at the 1-year follow-up. Finally, the OCTOBER study5 showed a reduction in the primary endpoint of death, myocardial infarction, and need for revascularization with OCT use in a selected group of complex lesions, such as true coronary bifurcations.

Q.: According to data from the activity registry of the Interventional Cardiology Association of the Spanish Society of Cardiology (ACI-SEC), intravascular imaging is used in 15% of patients treated with percutaneous revascularization. Do you think this new recommendation will increase that figure? What are the barriers to greater implementation of these techniques?

A.: The ACI-SEC activity registry data show a progressive and constant increase in the use of intracoronary imaging, such an increase, yet these data might not meet the expectations6 revealing an unequal adoption of imaging use across centers between 8% and 36%. Robust scientific evidence supporting the recent class I recommendation will undoubtedly have a positive impact on the use of imaging. However, several factors explain the underutilization of these imaging modalities. The first being time consumption: many cath labs handle a heavy caseload, and obtaining images usually increases procedural time. However, systematic use—losing the exceptional nature of imaging—reduces setup time and aids interpretation. Another significant factor is spending: increasingly higher financial allocations are needed for various unit procedures, and imaging is sometimes erroneously omitted as a cost-saving measure in coronary procedures. In this regard, the recent cost-effectiveness analysis conducted in the RENOVATE-COMPLEX-PCI study suggests that intracoronary imaging is more cost-effective than angiography alone in complex coronary lesions reducing cumulative medical spending and improving long-term quality of life.7

Q.: Although, in general, the new recommendation is indicated for complex lesions, it particularly highlights left main coronary artery disease, true bifurcations, and long lesions. Could you elaborate which lesions, in your opinion, would benefit most from the use of intravascular imaging in treatment?

A.: The greatest benefit of intracoronary imaging is observed in procedures associated with more adverse events during follow-up, such as complex lesions, particularly left main coronary artery disease, long coronary disease, and true bifurcations. Whether due to the technical complexity of the intervention or the greater myocardial area at risk, these scenarios yield the most significant benefit from imaging-guided coronary interventions. Future studies would help identify which patients and lesions benefit the most from intracoronary imaging and determine whether differences exist in outcomes between OCT and IVUS. The ILLUMIEN IV study8 sought to evaluate the impact of OCT not only on anatomically complex procedures but also on high-risk populations, such as diabetic patients. Although better stent expansion—minimal stent area—was demonstrated in the OCT-guided group, this did not translate into fewer clinical events compared with angiography at the 2-year follow-up.

Q.: The complexity of interventions is not only determined by anatomical complexity, as we know that there are clinical situations that impose challenges as well. In your opinion, what clinical scenarios or factors should encourage the use of intravascular imaging to optimize procedures?

A.: Traditionally, intracoronary imaging has been associated with guiding complex coronary interventions. However, imaging not only guides interventions but also the diagnosis of coronary artery disease, where it has been playing an increasingly prominent role. On the one hand, imaging is the gold standard in the etiological diagnosis of myocardial infarction with nonobstructive coronary arteries, which presents a major adverse event rate—death or reinfarction—of approximately 5% each year.9 On the other hand, there is growing scientific evidence of the prognostic impact of vulnerable plaques in non-culprit lesions, where intracoronary imaging is essential for evaluation purposes. While there are no current recommendations on which patients benefit from this analysis or what the therapeutic strategy should be, in the coming years, we’ll likely see a more global patient assessment for better risk stratification after a coronary event.

Q.: In general, when do you use intravascular imaging?

A.: The limitations of angiography—which provides only a 2-dimensional luminogram, are well-known. However, as previously mentioned, the greatest benefit of intracoronary imaging lies in the most complex lesions. Theferore, it seems prudent to use imaging in 4 specific scenarios: interventions on the left main coronary artery; stent failure—thrombosis or restenosis—chronic total occlusions; and calcified or ostial lesions. In all these scenarios, imaging characterizes the lesion, guides optimal stent implantation, and determines the percutaneous technique or tools needed during the procedure. However, equally important as the type of lesion is the timing of imaging use, which should be maximized early in the procedure rather than only to confirm a good result. Beyond its role in coronary intervention, imaging has a purely diagnostic utility, particularly in myocardial infarction with nonobstructive coronary arteries, where imaging—mainly OCT—establishes the etiological diagnosis in approximately 50% of the cases.

Q.: When you use imaging, when do you prefer IVUS and when OCT?

A: These techniques do not cancel each other out, but are complementary due to their technological differences. Their use should be adapted to each specific scenario while considering the operator experience and availability. OCT offers faster acquisition and has 10 times higher resolution than the IVUS, enabling clearer visualization of the intimal surface. This turns it into the imaging modality of choice for plaque characterization, especially when studying vulnerable plaques and stent failure. It is also the gold standard for calcium characterization, allowing the quantification of the arc and its thickness in most cases. IVUS, on the other hand, offers greater vessel depth visualization, including deeper layers in the absence of calcium, and does not require blood clearance for acquisition. This makes IVUS particularly useful for left main coronary artery disease, coronary dissection, chronic total occlusion interventions—where subintimal tracking discourages contrast use—and patients with chronic kidney disease, in whom contrast administration must be minimized.

Therefore, the results of the OCTIVUS study10 provided information on the comparative efficacy of OC-T and IVUS-guided coronary intervention. The 2 techniques can be used safe and effectively in most procedures, with comparable short- and long-term outcomes.

FUNDING

None declared.

STATEMENT ON THE USE OF ARTIFICIAL INTELLIGENCE

No artificial intelligence was used in the development of the concept of this manuscript.

CONFLICTS OF INTEREST

None declared.

REFERENCES

QUESTION: Clinical practice guidelines have raised the recommendation level for the use of intravascular imaging during percutaneous revascularization procedures for complex lesions to class I. Can you briefly explain the basis for this change?

ANSWER: The change of recommendation made in the European Society of Cardiology (ESC) guidelines to class I and evidence level A for the management of chronic coronary syndrome1 is based on 5 main references: 3 randomized clinical trials published in 2023 in the N Engl J Med,2-4 which included a total of 5327 patients, and 2 meta-analyses published in the J Am Coll Cardiol (2023)5 and Lancet (2024),6 with a total of 38,648 patients. These trials showed a reduction in major cardiovascular adverse events and target vessel failure compared with the angiography-guided procedure alone.

Although only 1 of the randomized clinical trials2 did not show statistically significant benefits in the clinical endpoint of target vessel failure, it did show improvements in stent minimal area assessment by imaging, which were significantly greater in patients treated with optical coherence tomography (OCT). The studies mentioned in the guidelines were conducted in populations with complex lesions, including bifurcations,3,4 chronic total occlusions,2,4 diffuse disease (≥ 38 mm² or ≥ 28 mm²), severe calcification,2,4 multivessel disease,4 diffuse restenosis,2 ostial lesions,4 and left main coronary artery disease.3,4 The rates of diabetic patients varied across studies (18%,3 28%,4 and 40%2), and high rates of acute coronary syndrome were reported (50%4 and 59.5%2).

The most recent meta-analysis5 with 15,964 patients allocated to intravascular ultrasound (IVUS) or OCT vs coronary angiography-guided angioplasty showed a 45% reduction in cardiac death, a 18% reduction in target vessel myocardial infarction, a 28% reduction in lesion revascularization, a 61% reduction in stent thrombosis, a 25% reduction in all-cause mortality, and a 17% reduction in global infarction, with no significant differences being reported between IVUS and OCT.

Q.: According to data from the activity registry of the Interventional Cardiology Association of the Spanish Society of Cardiology (ACI-SEC), intravascular imaging is used in 15% of patients treated with percutaneous revascularization. Do you think this new recommendation will increase that figure? What are the barriers to greater implementation of these techniques?

A.: In the 2023 ACI-SEC registry,7 intracoronary imaging and pressure wire-guided percutaneous coronary interventions (PCI) remain stable at around 15% of cases, with 7% corresponding to IVUS and 3% to OCT; similar figures to those from 2022, with a slight increase in OCT use. The new European guidelines recommendation should encourage its use. However, there may be initial barriers to its implementation, including:

• – Cost: cost-effectiveness analyses have shown that despite higher initial procedural costs, both IVUS and OCT are favorable in the mid- and long-term due to the reduction in adverse events and reinterventions.8-10
• – Procedural time: the incorporation of intracoronary imaging may extend PCI procedural time. Although this time has been significantly reduced compared with the early days of the technique,11,12 it can vary depending on factors such as coronary anatomy, intervention complexity, the experience of the heart team, and the existence of systematic analysis protocols. New automatic or semi-automatic analysis programs and co-registration can reduce analysis times and, substantially, aid decision-making.
• – Team training: training in the use of devices and intracoronary imaging analysis should be incorporated into both basic interventional cardiology training and continuing education programs. This will be essential to minimize the immediate minimal incremental risks associated with its use2 and make it a systematic tool. Its integration has the potential to significantly reduce adverse events such as cardiac death and target vessel failure.5

Q.: Although, in general, the new recommendation is indicated for complex lesions, it particularly highlights left main coronary artery disease, true bifurcations, and long lesions. Could you elaborate which lesions, in your opinion, would benefit most from the use of intravascular imaging in treatment?

A.: The new clinical practice guidelines on the management of chronic coronary syndrome support the use of intracoronary imaging based on the above-mentioned studies,2-6 in which, at least, 5327 patients exhibited complex lesions. This represents about a third of all 15,964 patients included in the most recent meta-analysis;6 however, it also included other studies with patients with complex lesions, such as long lesions, left main coronary artery disease, ST-segment elevation and non-ST-segment elevation myocardial infarctions, and chronic total occlusions, as well as patients with less complex lesions. With current evidence, there are scenarios—rather than individual lesions—where the use of intracoronary imaging should be considered essential, such as left main coronary artery disease, coronary artery occlusions, complex bifurcations, severely calcified coronary lesions, PCI-related complications, spontaneous coronary dissection requiring intervention, long lesions, lesions with a high thrombotic burden, target lesion failure, diabetic patients, and those with multivessel disease.

Q.: The complexity of interventions is not only determined by anatomical complexity, as we know that there are clinical situations that impose challenges as well. In your opinion, what clinical scenarios or factors should encourage the use of intravascular imaging to optimize procedures?

A.: The use of intracoronary imaging is supported in virtually all clinical scenarios. Although the ESC guidelines on the management of chronic coronary syndrome1 have formalized its recommendation, the meta-analyses supporting this indication include both chronic and acute clinical contexts and address most coronary artery lesions, from simple to highly complex. Moreover, integrating coronary physiology with intracoronary imaging could be a key element to optimize outcomes in percutaneous coronary treatment offering a more precise approach to the intervention.13

Q.: In general, when do you use intravascular imaging?

A.: In my routine clinical practice, I use intracoronary imaging primarily in complex PCI cases, such as left main coronary artery disease, diffuse disease, chronic total occlusions, bifurcations not treated with provisional stent techniques, or severely calcified coronary lesions, as well as in cases of treatment failure of previously treated segments and PCI-related complications. I foresee incorporating intracoronary imaging systematically in diabetic patients and in the planning of treatments with drug-eluting balloons to optimize results and further individualize the intervention strategy.

Q.: When you use imaging, when do you prefer IVUS and when OCT?

A.: In my everyday practice, I rather use IVUS for the evaluation of left coronary artery disease, in unstable patients, in those with renal insufficiency, in cases of high thrombotic burden, dissection, and for managing PCI-related complications. Conversely, I use the OCT in situations of target lesion failure, both in stents and in segments previously treated with drug-eluting balloons, in severely calcified coronary lesions, and in cases of diffuse disease, particularly in diabetic patients, in whom co-registration helps to more precisely delineate the segments that need to be treated.

FUNDING

None declared.

STATEMENT ON THE USE OF ARTIFICIAL INTELLIGENCE

No artificial intelligence was used in the development of the concept of this manuscript.

CONFLICTS OF INTEREST

None declared.

REFERENCES

QUESTION: We would like to know your interpretation of the PREVENT trial.1 Do you think it could change clinical practice regarding the treatment of vulnerable plaques?

ANSWER: The PREVENT is the first clinical trial ever conducted with statistical power to detect clinical differences in preventive treatment with stent implantation in functionally non-significant vulnerable plaques (fractional flow reserve [FFR] > 0.80, obtained via intracoronary pressure wire).1 This trial included patients with vulnerable plaques diagnosed using various intracoronary imaging modalities, who were randomized to receive stent implantation or optimal medical therapy. Approximately 2000 out of the 5500 lesions evaluated in the study were functionally significant (FFR ≤ 0.80), while 1600 (45%) out the remaining functionally non-significant 3500 lesions had vulnerable plaque criteria and were included in the study. The primary endpoint at the 2-year follow-up—a composite of cardiac death, target vessel myocardial infarction, target vessel revascularization, or hospitalization for unstable angina—was observed in 0.4% of the intervention group and 3.4% of the control group (a statistically significant difference). Despite this favorable result, the PREVENT trial has important limitations that raise questions on the implementation of this practice in everyday life.

First, more than 80% of the patients from the PREVENT trial were included with a chronic coronary syndrome (CCS). If we admit that the reason behind preventive treatment with stent implantation in vulnerable plaques is to prevent the rupture of the plaque and, therefore, reduce the risk of an acute coronary syndrome (ACS), then a population with low risk of ischemic events has been included at the follow-up. The CLARIFY registry2 helps us to put into context the residual risk of a properly treated coronary patient. In this registry with 32,000 patients, the risk of non-fatal myocardial infarction or cardiac death for those with CCS who had never experienced an ACS was 6.4% (9.1% at the 5-year follow-up for those with a history of myocardial infarction, which is a statistically significant difference).

Second, in the PREVENT trial, a total of 3 different intracoronary imaging modalities were used for the diagnosis of vulnerable plaques, any of them at the discretion of the operator performing the test based on their experience: intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS), or optical coherence tomography (OCT). Furthermore, different criteria for vulnerable plaques were marked depending on the imaging modality used, which very likely included multiple anatomical types of plaques. In general, almost 60% of all vulnerable plaques included were defined with IVUS by a minimum luminal area < 4 mm2 and a plaque burden > 70%, with no mention of plaque composition. We know that most lesions causing ACS are fibro-lipid plaques with rupture of the (thin) fibrous cap covering their necrotic core.3 Fibrous plaques, thick-capped fibro-lipid plaques, or fibrocalcific plaques do not usually trigger ACS and are more associated with CCS. Probably, in the PREVENT trial, preventive stent implantation was overused for many plaques that did not meet these vulnerable plaque requirements after the use of an inappropriate intravascular imaging modality and choosing vulnerable plaque criteria that do not correspond to the types of plaques that can cause ACS.

Finally, in the PREVENT trial, all clinical benefit observed in favor of the mechanical treatment of vulnerable plaques derived from a reduction in the number of revascularizations and hospitalizations for unstable angina, without any significant differences being reported in the risk of non-fatal myocardial infarction or cardiac death, even at the 7-year follow-up. In the FAME 1 trial,4 which included patients with CCS and multivessel coronary artery disease, we learned that FFR-guided coronary revascularization reduces the number of lesions to be treated by around 40%, and that the optimal medical therapy—without stent—of these functionally non-significant lesions has similar efficacy to the revascularization of all angiography-guided only lesions in addition to being safe and cost-effective at the 5-year follow-up. Going back to the PREVENT trial, the preventive and elective revascularization of 45% of functionally non-significant lesions (FFR > 0.80) with criteria of vulnerable plaque to prevent only 3% of clinically driven target lesion revascularizations at the 7-year follow-up does not seem to offer a great clinical benefit and raises questions about cost-effectiveness. To change clinical practice, results with reductions in non-fatal myocardial infarction and cardiac death at the follow-up are needed.

Q.: Very briefly, what is the current state of evidence on the mechanical treatment of coronary plaques that do not compromise flow but show characteristics of vulnerability?

A.: Scientific evidence on preventive stent implantation in functionally non-significant coronary plaques with characteristics of vulnerable plaque is scarce. Post-hoc studies with patients assessed with OCT before stent implantation and at the follow-up show that stent implantation on thin fibrous cap fibroatheroma plaques—also known as vulnerable plaques—induces scarring of the neointima surrounding the struts, thickening of the fibrous cap, and potentially reduces the risk of plaque rupture.5

To date, only 2 prospective, randomized trials have investigated the utility of stenting on vulnerable plaques: the PROSPECT-ABSORB6 and PREVENT1 clinical trials. These 2 trials found significant differences in favor of mechanical intervention. However, as already mentioned, these trials have important limitations regarding the number of patients included (< 2000 combined), the intracoronary imaging modality used to define vulnerable plaque (mainly IVUS), and the endpoints that are not adequate to assess efficacy (clinical benefit obtained by reducing the need for revascularization, not the rate of non-fatal myocardial infarction or cardiac death).

A pilot study on the use of drug-coated balloons for treating vulnerable plaques—the DEBuT-LRP7 trial7—is also worth mentioning. This trial included a total of 18 patients who were assessed with NIRS during the index procedure and at the 9-month follow-up, and whose results showed that the amount of lipid decreased without affecting lumen size. However, much more evidence will be needed before recommending this treatment for vulnerable plaques.

Q.: In your opinion, in current clinical practice, which patients would be eligible for this strategy, if any?

A.: There is no clear answer to this question. What we do know is that atherosclerosis is a progressive disease. Patients with a past medical history of coronary artery disease who do not receive lipid-lowering therapy or receive non-intensive lipid-lowering therapy show plaque progression of, approximately, 1% every 2 years.8,9 It is estimated that only 65% of the patients on intensive lipid-lowering therapy capable of reducing low-density lipoprotein (LDL) cholesterol to < 70 mg/dL manage to stop the rate of lipid accumulation and even reduce the percent atheroma volume in serial IVUS assessments.8,10 Of note that more marked reductions in LDL cholesterol are associated with changes in the plaque composition and thickening of the fibrous cap of vulnerable plaques in serial OCT assessments.11 For these reasons, the latest clinical practice guidelines recommend reducing LDL cholesterol levels to < 55 mg/dL in patients with a history of clinical signs of atherosclerotic disease and < 40 mg/dL in patients with recurrent clinical events.12

However, in our setting, the percentage of patients who reach guideline-recommended levels is only around 30% (even lower in very high-risk patients).13 Therefore, although prioritizing the implementation of guideline-recommended intensive lipid-lowering therapies in the real world according to clinical practice is essential, we must acknowledge that, in many patients, these therapies will prove insufficient, especially in those with ACS.

In my opinion, patients with ACS are the best population for considering this strategy of mechanical stabilization of vulnerable plaques. ACS patients due to a ruptured plaque have an aggressive type of atherosclerosis with a massive plaque burden and more vulnerable plaques than patients with CCS,3 which makes them ideal candidates for the “hunt” of vulnerable plaques using intravascular imaging modalities of the infarct-related culprit artery and the rest of the vessels.

Q.: Briefly explain the VULNERABLE trial, which you lead along with Enrique Gutiérrez Ibañes and its current status.

A.: The Spanish Society of Cardiology Working Group on Intracoronary Diagnostic Techniques has promoted the conduct of the randomized, controlled, and single-blind VULNERABLE trial14 with more than 40 Spanish centers. This trial aims to evaluate around 2000 patients with ST-elevation myocardial infarction and angiographically intermediate non-culprit lesions (percent diameter stenosis of 40% up to 69%). All amenable lesions will be interrogated with a pressure wire, and those with FFR ≤ 0.80 will be stented and considered selection failures. The rest of the lesions (FFR > 0.80) will be investigated by OCT looking for characteristics of vulnerability. Although the lesions that do not meet characteristics of vulnerability will be managed medically, they will receive periodic follow-ups to assess adverse events (within the so-called VULNERABLE Registry). Finally, the study intends to include a total of 600 lesions with negative FFR but with characteristics of vulnerability according to the OCT, which will be randomized on a 1:1 ratio to stent implantation or optimal medical therapy (within the VULNERABLE trial). There is a 4-year planned follow-up for the patients of the registry and trial. The VULNERABLE is the first trial ever conducted with statistical power to assess the clinical benefit of preventive stent implantation on non-culprit lesions with characteristics of vulnerability according to the OCT, which in our opinion is the best intracoronary imaging modality to diagnose these types of plaques.

FUNDING

None declared.

DECLARATION ON THE USE OF ARTIFICIAL INTELLIGENCE

No artificial intelligence has been used.

CONFLICTS OF INTEREST

None declared.

REFERENCES