The future of interventional cardiology

Balloon failure during percutaneous coronary intervention (PCI), which occurs particularly in severely stenotic and extensively calcified lesions, remains one of the most complex and frustrating scenarios for the interventional cardiologist. In addition, initial balloon failure is associated with prolonged procedures, greater resource consumption, and an increased risk of complications.1 All this occurs despite the development and availability of different plaque-modification techniques, including excimer laser coronary atherectomy (ELCA).2,3

Across different studies over the years, the concept of balloon failure has encompassed various scenarios, including both uncrossable and undilatable lesions. This terminological imprecision may affect the interpretation of the available results from these studies, which in turn may have an impact on decision-making in clinical practice.

In the context of PCI for complex uncrossable or undilatable lesions, a better understanding of the underlying anatomical mechanisms is essential. This may be facilitated by a more systematic use of intracoronary imaging modalities. Nevertheless, dedicated studies in this setting are clearly needed. Their results may help improve lesion characterization and optimize the therapeutic approach through more appropriate selection of plaque-modification techniques.2,3

In a recent article published in REC: Interventional Cardiology, Jurado-Román et al.4 present the design of the LUDICO study (Coronary laser in undilatable and uncrossable lesions; NCT07206082), a prospective, multicenter, single-arm observational trial to evaluate the safety and efficacy profile of ELCA in 230 patients with an indication for PCI and lesions in which balloon failure has occurred. The main strength of the study lies in its methodological approach, as it explicitly distinguishes between uncrossable and undilatable lesions. This distinction may contribute to a better understanding of the role and positioning of this technique, given that in both scenarios—after failure to cross or dilate the lesion with a balloon—ELCA would represent the first plaque-modification strategy to be used. Another relevant aspect of the study is the recommendation to use intracoronary imaging, specifically optical coherence tomography. This approach allows assessment not only of procedural success but also of the structural changes induced in the lesion. Currently, these changes have been poorly characterized in the context of ELCA, particularly in cases of in-stent restenosis.5

The most evident limitation of the study, appropriately acknowledged by the authors, is the absence of a control group, which makes direct comparison with other plaque-modification techniques impossible. A comparison between these techniques has recently been performed in PCI for complex lesions in the randomized ROLLERCOASTR-EPIC22 study (Rotational atherectomy, lithotripsy or laser for the treatment of calcified stenosis).6 Such a comparison could also have been of interest in the specific context of the study under discussion. Another aspect worth noting is that the definition of an undilatable lesion is based on an objective criterion (balloon expansion < 80% after 1:1 noncompliant balloon inflation at 18 atm). In contrast, a stricter or more precise definition of an uncrossable lesion is lacking. In this study, an uncrossable lesion was defined after failure to advance a low-profile balloon despite adequate guide support at the operator’s discretion. This approach may introduce a degree of variability that should be considered when interpreting the results.

From a broader perspective, the use of ELCA in clinical practice remains limited. This may be partly explained, in addition to the relatively scarce scientific evidence, by a certain paradox: although the technique is technically straightforward from the operator’s standpoint, its application entails a degree of conceptual complexity. Specifically, the procedural parameters must be adjusted according to the clinical scenario in which the device is used. This may help explain its relatively limited adoption in catheterization laboratories across Spain.6 Indeed, the safety and efficacy of ELCA largely depend on several procedural decisions that remain incompletely standardized. These include the optimal timing of ELCA use during the procedure, the selection of catheter diameter, the potential combination with other plaque-modification techniques, and the appropriate selection and modulation of device parameters. These parameters include energy intensity and frequency, application duration, total number of pulses, and even the adjunctive use of contrast medium (amplification).7 Table 1 proposes a practical framework for adjusting ELCA parameters according to the clinical context in which it is used. In conclusion, although ELCA is not technically demanding from an operator-handling perspective, its optimal use requires a certain degree of experience. Maximizing its benefits depends on a thorough understanding of the predominant mechanism underlying each lesion, a process that can be facilitated by the performance and appropriate interpretation of intracoronary imaging.

Table 1. Proposed excimer laser configuration in different scenarios

Clinical scenario	Frequency (Hz)	Energy (mJ/mm2)	Adjunctive use of contrast	Practical comments
Underexpanded stent	60-80 (high)	60–80 (high)	No, according to device labeling. Observational studies support the usefulness of contrast amplification in lesions resistant to ELCA with saline solution	Start with high parameters if saline solution is used. If contrast is used, it is prudent to initially reduce ELCA parameters (frequency 25–40 Hz, energy 30–45 mJ/mm2), and they may be progressively increased with caution
Severely calcified lesion	60-80 (high)	60–80 (high)	No, according to device labeling. Limited evidence supports the potential usefulness of contrast in lesions resistant to ELCA with saline solution	Start with high parameters if saline solution is used. The use of contrast is not well established; if used, it is reasonable to consider an initial reduction in frequency and energy, which may then be progressively increased with caution
Thrombotic lesion	25-40 (low/medium)	30–60 (low/medium)	No	In “pure” thrombotic lesions, low energy and frequency are generally sufficient. In cases of thrombus with a large plaque burden, energy and frequency parameters may be gradually increased
ELCA, excimer laser coronary angioplasty.

When examining the available evidence on ELCA, which remains generally limited, the technique has demonstrated clearer usefulness in certain specific scenarios.8 One of these is the treatment of uncrossable lesions,9 in which ELCA can advance over the same angioplasty guidewire. This represents a clear advantage and suggests that ELCA could be considered one of the preferred plaque-modification techniques in this setting. Moreover, ELCA may facilitate subsequent device advancement in extremely hostile anatomies and assist in the management of undilatable lesions, particularly those related to stent underexpansion. In these cases, its ability to modify both the underlying plaque and resistant neointimal tissue may allow more effective subsequent expansion.10 In another challenging scenario—the treatment of lesions with a high thrombotic burden—ELCA has also shown potential usefulness.11 Supporting this application, a contemporary series of patients undergoing primary PCI demonstrated that ELCA can “vaporize” thrombotic material, reducing it to microscopic particles and improving coronary flow, thereby facilitating safer and more effective stent implantation.12

FUNDING

None declared.

CONFLICTS OF INTEREST

A. Pernigotti declares having received consulting fees from Iberhospitex and B.Braun. M. Mohandes declares having received consulting fees from Philips. J.L. Ferreiro declares having received speaker or consulting fees from Eli Lilly Co, Daiichi Sankyo, Inc., AstraZeneca, Pfizer, Abbott, Boston Scientific, Boehringer Ingelheim, Bristol-Myers Squibb, Rovi, Terumo, Sahajanand Medical Tech- nologies, Iberhospitex, and Ferrer, and a research grant from AstraZeneca.

REFERENCES

Since its incorporation into routine clinical practice more than 20 years ago, transcatheter aortic valve implantation (TAVI) has progressively gained acceptance within the cardiology community, driven by a successful and comprehensive clinical program that began with early reports in inoperable1 and high-risk patients,2 around 2010.

From the earliest studies, patient eligibility for TAVI was determined by a multidisciplinary committee of cardiologists and surgeons— which came to be known as the heart team—and procedures were performed exclusively at centers with on-site cardiac surgery. Similarly, all subsequent clinical practice guidelines on the management of TAVI have assigned the highest level of recommendation to performing the procedure in centers with a heart team and on-site cardiac surgery, a requirement that has persisted through the most recent European clinical practice guidelines.3

On the other hand, the marked increase in the number of procedures is making it difficult for hospitals with on-site cardiac surgery to meet this growing demand, thereby considerably prolonging waiting times—an especially sensitive issue given the high mortality rate of patients in this situation, which may exceed 15%.4 Therefore, it may be time to ask the following question: is the presence of a cardiac surgery department at the center still a prerequisite for establishing a TAVI program?

In an article published in REC: Interventional Cardiology, Rocha de Almeida et al.5 present their experience with 300 patients undergoing TAVI at a center without on-site cardiac surgery. Despite the absence of on-site cardiac surgery, what is striking at first glance is that this is a regional referral center with an interventional team experienced in performing the procedure at high-volume centers. Thus, this represents an initial experience for the center, but not for its operators.

In this series of 300 TAVI procedures performed over approximately 4 years, outcomes were comparable to those of high-volume centers; despite an advanced mean age (82 years), a mean Society of Thoracic Surgeons (STS) score of 3.8, and 17% of patients being categorized as high risk (STS score > 8), the 30-day mortality rate (primary endpoint) was 3.7% and the in-hospital mortality rate, 2%, with no conversions to surgery, annular rupture, coronary obstruction, or prosthetic embolization, and only 2 cases of percutaneous pericardiocentesis were required due to guidewire perforation.5

In fact, compared with the Portuguese registry,6 the 30-day mortality rate was numerically lower (3.7% vs 4.8%; P = not significant [NS]), as was the stroke rate (2.7% vs 4.6%; P = NS), with similar rates of bailout cardiac surgery (0 vs 0.4%), comparable vascular complications (8% vs 6.8%; P = NS), and an identical rate of permanent pacemaker implantation (20% vs 19%).

Similar experiences have been reported in the literature from other countries, with varying sample sizes and generally retrospective designs (table 1). The earliest published experience of TAVI without on-site cardiac surgery was reported by Eggebrecht et al.7,9 using data from the German registry and comparing the outcomes at centers with a “visiting” surgeon with those obtained at centers with on-site cardiac surgery, without any differences being reported in the 30-day mortality rate (6.2% vs 8.3%; P = NS) and with very low rates of bailout surgery (2.2% vs 1.6%). This experience has been replicated in other countries, such as Austria,8 with similar mortality rates in centers with and without on-site cardiac surgery (6.9% vs 6.2%; P = NS), and Spain,10 with a comparable 30-day mortality rate (6.1%) and a very low rate of bailout surgery (0.3%). In more recent registries including lower-risk patients, such as the Israeli experience,11 the 30-day mortality rate can be as low as < 1%.

Table 1. Studies on TAVI in centers with and without on-site cardiac surgery

Study	Country	Patients		Vascular complications		30-day mortality rate		Bailout surgery
		In centers without on-site cardiac surgery (n)	In centers with on-site cardiac surgery (n)	In centers without on-site cardiac surgery (%)	In centers with on-site cardiac surgery (%)	In centers without on-site cardiac surgery (%)	In centers with on-site cardiac surgery (%)	In centers without on-site cardiac surgery (%)	In centers with on-site cardiac surgery (%)
Eggebrecht et al.7	Germany	178	1754	18.5	22.2	6.2	8.3	2.2	1.5
Egger et al.8	Austria	290	290	9.3	4.8	6.9	6.2	—	—
Eggebrecht et al.9	Germany	550	550	—	—	1.8*	2.9*	—	—
Roa Garrido et al.10	Spain	384	—	—	—	6.1	—	0.3	—
Barashi et al.11	Israel	149	—	0.67	—	0.67	—	0	—
*In-hospital mortality.

As optimistic as these registries may appear when initiating a TAVI program without on-site cardiac surgery, the importance of care organization for this purpose must not be overlooked. High-volume centers with on-site cardiac surgery have the advantage of hospital-wide adaptation to this type of procedure, as well as training of all involved specialties, including cardiology, cardiac surgery, anesthesia, and intensive care. The authors highlight two critically important aspects: when they initiated the program, they already had extensive experience in TAVI, and the center served as a regional cardiology referral institution. Assuming that a TAVI program without on-site surgery can be initiated without all necessary safeguards would simply place patients at risk.

A notable feature of contemporary practice is that refinement of procedural steps, improvements in materials, enhanced team training, and supervision by experienced operators during program initiation have resulted in excellent TAVI and very low complication rates,12 particularly in patients with low STS scores. Furthermore, performing this procedure at centers without on-site surgery has different implications in high-risk patients with limited surgical bailout options than in low-risk patients, in whom bailout surgery remains feasible, although infrequent and usually associated with unfavorable outcomes.12 Therefore, careful patient selection appears mandatory, with the participation of a heart team capable of determining eligibilty for TAVI at centers without on-site surgery and auditing outcomes.

Further insight may be provided by the new prospective Italian registry TAVI at Home,13 which will include a total of 200 patients undergoing TAVI at centers without on-site surgery under strict inclusion and exclusion criteria (> 75 years, high or prohibitive risk, non-bicuspid valves, and no degenerated surgical valves) always under the scrutiny of a heart team including cardiac surgeons, clinical cardiologists, interventional cardiologists, imaging specialists, and anesthesiologists.

Moreover, in Italy, the randomized TRACS trial is underway, comparing TAVI performed at centers with vs without on-site cardiac surgery,14 with a planned enrollment of 566 patients and inclusion and exclusion criteria very similar to those of the TAVI at Home registry.

In conclusion, and in response to the question posed in this editorial, we firmly believe that performing TAVI at centers without on-site cardiac surgery is, without question, a necessary step. Accordingly, strict requirements and systematic outcome auditing are essential to ensure that this necessity does not translate into undue risk.

FUNDING

None declared.

CONFLICTS OF INTEREST

None declared.

REFERENCES

The comprehensive management of patients with congenital heart disease is one of the major challenges in contemporary cardiology. In its early stages, the management of these patients was based primarily on diagnosis and palliative care. Afterwards, the goal shifted to ensuring survival, and, currently, the challenge is for patients to reach adulthood with good quality of life, minimizing morbidity associated with their congenital heart condition and prior procedures, while ensuring structured follow-up.

The major shift came from 2 parallel revolutions: advances in diagnostic capability and structural heart procedures. Due to developments in echocardiography, magnetic resonance imaging, and computed tomography, early and precise diagnosis is now possible—even in utero—allowing clinicians to properly inform families about the diagnosis and prognosis of these conditions. At the same time, surgical advances and, notably, significant progress made in percutaneous coronary interventions have transformed the natural course of this disease.

Cardiac catheterization, initially conceived as a diagnostic tool, soon acquired a decisive therapeutic role. In 1953, Rubio Álvarez et al.1 performed the first balloon valvulotomy. A decade later, Rashkind and Miller2 described atrial septostomy. These milestones marked the beginning of percutaneous coronary intervention, first as a palliative therapy and later as an established therapeutic option. Currently, many patients avoid surgery, lengths of stay are shorter, recovery is faster, and percutaneous coronary intervention has become a well-established, safe, and effective alternative.3

Percutaneous procedures are now the first-line therapy for obstructive lesions (valvular stenosis, aortic coarctation, etc.) and closure of septal defects and ducts (patent ductus arteriosus). Moreover, these procedures often serve as essential adjuncts in the management of complex congenital heart disease, including in patients with single-ventricle physiology who have undergone cavopulmonary diversion techniques.

In Spain, hemodynamic activity in congenital heart disease is distributed across 3 different types of cath lab based on the profile of the patients: pediatric labs (primarily for patients < 18 years), adult labs (primarily for patients ≥ 18 years), and mixed labs (no age distinction), which in some cases differ by working teams. Diagnostic catheterization remains the most frequently performed procedure, especially in adult cath labs accounting for 65% of cases.4

With increasing survival, a growing number of patients with congenital heart disease reach adulthood, creating the need for repeated diagnostic and therapeutic catheterizations, which are often prolonged and technically complex. Optimal management requires integrating a deep understanding of congenital heart disease pathophysiology with expertise in vascular complications typical of adulthood.

The complexity of many scenarios—both biventricular (eg, tetralogy of Fallot, pulmonary atresia with ventricular septal defect, or transposition of the great arteries repaired with atrial or arterial switch) and single-ventricle anatomies (various forms of cavopulmonary diversion)—requires more than just technology: it demands true collaboration among teams. Cumulative experience demonstrates that the combined expertise of pediatric and adult interventional cardiologists generates irreplaceable added value. The pediatric interventional cardiologist contributes knowledge on congenital physiology, long-term disease progression, and complications associated with palliative or corrective procedures performed throughout life, whereas the adult interventional cardiologist contributes experience with device technology and vascular access issues typical of older patients.

Although this synergy benefits most clinical scenarios, it is especially relevant in the following:

• – Closure of complex defects: sinus venosus atrial septal defects (associated with anomalous pulmonary venous drainage), ventricular septal defects, persistent ductus arteriosus in adults with pulmonary hypertension or calcification, and dehiscence of surgical conduits (mainly in patients with atrial switch procedures for transposition of the great arteries).
• – Treatment of obstructive lesions: aortic coarctation (especially in patients with prior childhood procedures); stenosis of surgically placed conduits (atrial switch procedures for transposition of the great arteries or right ventricle–to–pulmonary artery conduits); or treatment of branch pulmonary arteries with angioplasty with or without stenting.
• – Pulmonary valve procedures: this is a rapidly expanding field in which the incorporation of multiple techniques now allows treatment of dilated right ventricular outflow tracts resulting from childhood surgical procedures, with excellent results comparable to surgery but with reduced procedural morbidity.5 Therefore, techniques involving stenting in dilated outflow tracts allow subsequent placement of balloon-expandable valves with excellent outcomes. However, the major forthcoming advance is the consolidation of self-expandable valves, which simplify valve implantation. In these situations, the experience of adult interventional cardiologists with self-expandable valves in other settings, such as aortic valve procedures, is highly valuable.
• – Evaluation of single-ventricle physiology: it requires repeated cardiac catheterizations from the earliest stages of life. The pediatric interventional cardiologist contributes not only essential insight into the underlying pathophysiology but also expertise in managing complications associated with single-ventricle physiology and the palliative procedures needed to help patients reach adulthood in the best possible functional condition. Consequently, these patients often undergo interventions for stenosis of palliative conduits or branch pulmonary arteries, closure of systemic–pulmonary collaterals, or optimization of Fontan circulation through creation or closure of fenestrations.6
• – Coronary anomalies and complications: the adult interventional cardiologist plays a crucial role, as experience in areas such as atherosclerotic disease is invaluable in addressing and treating coronary anomalies percutaneously.

In our setting, the joint work model established since 2015 between pediatric and adult teams illustrates this philosophy. It is not just about sharing a cath lab but generating shared spaces for discussion and decision-making through multidisciplinary clinical sessions to standardize criteria and enable individualized strategy planning. A recent example reflecting the benefits of this collaborative model is a Fontan optimization case involving stenting and collateral closure. The patient was a 41-year-old woman with complex congenital heart disease and single-ventricle physiology—characterized by atrioventricular concordance with ventriculoarterial discordance, complete transposition of the great arteries, a large ventricular septal defect, pulmonary stenosis, and right ventricular hypoplasia—who had undergone multiple surgical procedures (Blalock–Taussig shunt at 13 months, systemic–pulmonary shunt at 2.5 years, bidirectional Glenn at 9 years, and extracardiac Fontan at 17 years). She exhibited reduced functional capacity and Fontan-associated hepatopathy. Cardiac catheterization confirmed a severely calcified Fontan conduit with significant stenosis at its insertion into the right pulmonary artery. Balloon sizing was performed, followed by implantation of a covered stent postdilated with a 20-mm balloon, achieving a good result. A marked stenosis at the Glenn-to–right pulmonary artery anastomosis was confirmed via right internal jugular vein, and a 34 mm bare-metal stent was implanted (figure 1A,B). The aortography performed via arterial access revealed the presence of large aortopulmonary collaterals supplying the 2 upper lung lobes, which were successfully occluded. The first one, toward the right and left upper lobes, was closed using an Amplatzer Vascular Plug 4 (Abbott Cardiovascular, United States) and coils; the second, toward the right upper lobe, was also closed with an Amplatzer Vascular Plug 4 and coils (figure 1C,F). This case illustrates the synergy between pediatric and adult interventional cardiologists in completing treatment.

Figure 1. Fontan optimization. A: stenosis at the Glenn–right pulmonary artery anastomosis. B: bare-metal stent implanted in the stenosis. C: large aortopulmonary collateral supplying the right and left upper lung lobes. D: occlusion of this collateral. E: large aortopulmonary collateral supplying the right upper lobe. F: occlusion of the collateral.

The increasing number of adults with congenital heart disease has led to more frequent, longer, and technically demanding procedures, requiring combined expertise in congenital heart disease and adult vascular complications. The joint cath-lab model for congenital heart disease should be promoted to facilitate individualized case discussion and procedural planning, both of which are essential for therapeutic success. Cross-disciplinary training and communication among teams are critical to establishing a modern, collaborative approach to interventional care in congenital heart disease. The European clinical practice guidelines on the management of adult congenital heart disease emphasize the importance of a structured transition and the need for multidisciplinary heart teams.7 Furthermore, studies show that long-term outcomes improve significantly in centers with combined pediatric and adult experience.5

The field of congenital heart disease reminds us that progress does not come from isolated disciplines, but from shared effort. The current challenge is no longer simply to extend life, but to ensure its quality. Therefore, integration of pediatric and adult cardiology in the interventional management of congenital heart disease is no longer optional, but essential.

FUNDING

None declared.

ETHICAL CONSIDERATIONS

Informed consent was obtained from the patient described in the case, including approval for publication.

CONFLICTS OF INTEREST

None declared.

ACKNOWLEDGMENTS

The authors thank Dr. Pastora Gallego and Dr. José F. Díaz Fernández for their collaboration in reviewing the manuscript.

REFERENCES

Currently, invasive coronary angiography is still the main technique to identify obstructive coronary artery disease. However, its diagnostic yield is limited by its inability to assess the functional relevance of intermediate stenoses.1 The introduction of pressure guidewire-based physiological assessment was first enabled by the development of fractional flow reserve (FFR).2 Within the following decade, a large body of evidence supported the benefit of FFR in revascularization decision-making, leading to its endorsement by clinical practice guidelines.3-5 Still, a low penetrance of FFR was observed, due to scepticism in coronary physiology, the need for coronary instrumentation, adenosine infusion, and increased procedural time and costs.6 These challenges led to the development of several non-hyperemic indices, avoiding the need for hyperemic agents, as well as angiography-derived physiological assessment techniques (ADPAT), which avoid both the use of adenosine and coronary guidewires. Over the past few years, several ADPAT modalities have emerged with the objective of estimating FFR by combining fluid dynamic equations, 3D models of the coronary tree and certain predefined boundary flow conditions.7

Most ADPAT have pivotal validation studies that compare them to FFR showing good diagnostic accuracy. Among these methods, quantitative flow ratio (QFR) has been evaluated in the largest number of studies and, importantly, the main clinical trials powered for cardiovascular events. In the randomized FAVOR III China trial, the QFR-guided revascularization of intermediate stenoses was superior to angiography-guided revascularization,8 prompting a 1B recommendation for the use of QFR by the European clinical practice guidelines on the management of chronic coronary syndromes.9 However, when QFR was compared with FFR for clinical events in the randomized FAVOR III Europe trial it not only failed to show non-inferiority, but also had a significantly worse rate of adverse events, with a hazard ratio of 1.67 for the composite primary endpoint and 1.84 for myocardial infarction (MI).10 This has raised concerns about the reliability of QFR and its applicability as a substitute for FFR in the routine clinical practice. Figure 1 illustrates the known advantages and disadvantages of ADPAT.

Figure 1. Advantages and disadvantages of ADPAT. ADPAT, angiography- derived physiological assessment techniques; FFR, fractional flow reserve; PCI, percutaneous coronary intervention.

In a recent article published in REC: Interventional Cardiology, Ruiz-Ruiz et al. provide a meta-analysis on the combined and individual accuracy of the most frequently used ADPAT software in the setting of functional interrogation of intermediate stenoses.11 After applying eligibility criteria, a total of 27 papers were finally selected, including more than 4800 patients and more than 5400 vessel analysis. Although stable angina was the most prevalent indication, roughly a third of the patients exhibited acute coronary syndromes, mostly unstable angina. In more than half of the cases, the target vessel was the left anterior descending coronary artery. The ADPAT modalities included primarily QFR; 42.6% of vessels), angiography-derived FFR (15.5%), and vessel FFR (12.0%).

The main results from the meta-analysis suggest a good diagnostic performance of the different ADPAT tools considered vs FFR. Overall sensitivity and positive predictive value were around 85%, whereas total specificity and negative predictive value exceeded 90%, highlighting a potential value of these techniques to identify functionally non-significant stenoses and defer revascularization. The area under the curve for predicting a significant FFR was remarkable (0.947). However, evidence quality on every ADPAT software was uneven and a large proportion of pivotal studies was included in the meta-analysis, precluding the results to properly represent a real-world patients’ population. Furthermore, there were several exclusion criteria, such as > 10% prevalence of previous surgical revascularization, > 25% prevalence of atrial fibrillation, or > 30% of the patients exhibiting MI if time from the event to physiological evaluation was not specified, which means the studies included are highly selected and may not accurately reflect our routine clinical practice.

In any case, taken at face, these data of diagnostic accuracy for ADPAT seem encouraging. The pressure wire-based instantaneous wave-free ratio (iFR) demonstrated an area under the curve, as well as positive and negative predictive values very similar to those reported in this meta-analysis for ADPAT.12 This would be indicative of a similar clinical value, which is why the negative results of the FAVOR III Europe trial came as such a shock. It is well established for FFR and iFR that much of the clinical benefit of physiology-based revascularisation derives from deferral of unneeded coronary interventions.13 Similarly, the advantage of QFR over angiography in the FAVOR III China trial was associated with a lower number of lesions treated in the QFR arm.8 However, data from the FAVOR III Europe trial questioned the ability of QFR to defer as many revascularizations as FFR. In this trial, median QFR values were lower than those of FFR, leading to more than 20% additional patients undergoing revascularization in the QFR group.10 On the other hand, it could be that the inaccuracy goes both ways: a post hoc subanalysis of the trial revealed that QFR-based intervention deferral was associated with worse outcomes, especially in terms of unplanned revascularizations.14 This suggests that excess events in the QFR arm of FAVOR III Europe trial might be attributed to both false positive and false negative measurements. For reproducibility, a pre-specified sub-study of the trial compared investigator-performed QFR measurements with repeated assessments by the core laboratory. Almost 30% disagreement was documented, including both significant and non-significant QFR values.15 Of note, the study included a rigorous training and certification protocol for all the investigators involved in QFR assessment.

Clearly, the final word on these techniques has not yet been written. If we aim to predict and reduce the risk of adverse cardiovascular events, both microvascular dysfunction and plaque vulnerability are 2 factors that we should taken into consideration. The former, not only modifies the risk of cardiovascular events, but affects the accuracy of ADPAT measurements.16 The latter is a major driver of adverse coronary events, may prompt percutaneous revascularization even in physiologically non-significant lesions,17,18 and cannot be accurately estimated by any angiographic technique. In this regard, the use of intravascular imaging to assess both plaque vulnerability and physiological significance by means of dedicated algorithms seems promising.19,20 Another important unsolved issue is the performance of physiology –of any kind– in clinical scenarios other than chronic coronary syndrome. Current clinical practice guidelines from the European Society of Cardiology do not support the use of FFR in ST-segment elevation MI due to conflicting evidence, and all other physiological indexes are lacking clinical trials in this setting. Of note, MI with and without ST-segment elevation accounts for more than half of revascularization procedures in most centers with a primary percutaneous coronary intervention program in our setting. The ongoing VULNERABLE trial18 should shed light on this issue of whether physiology is sufficient to safely defer non-culprit lesions in ST-segment elevation MI, or rather a more proactive approach is needed to detect and treat vulnerable plaques. As we wait for the results of this and other trials, integrative efforts such as the meta-analysis conducted by Ruiz-Ruiz et al.11 may contribute to expand knowledge and expertise on ADPAT.

FUNDING

None declared.

CONFLICTS OF INTEREST

None declared.

REFERENCES