The future of interventional cardiology

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

We have witnessed a remarkable evolution in the field of percutaneous coronary intervention (PCI) over the past half a century, transitioning from the first cases of balloon angioplasty to bare metal stents and, most notably, to the widespread use of drug-eluting stents (DES). The advent of DES substantially reduced restenosis rates by providing a mechanical scaffold combined with sustained release of an antiproliferative drug, eg, taxanes and then rapamycin derivatives. Considering their permanent and static nature, such metallic implants are not without limitations, including the potential for delayed healing, chronic inflammation, inhibition of positive vessel remodeling, and the need for prolonged antithrombotic therapy.1,2 Following this, the concept of bioresorbable vascular scaffolds emerged, promising a temporary scaffold that would “leave nothing behind”. Nonetheless, their initial promise was hampered by late scaffold thrombosis and a high rate of target lesion failure.3 At the same time, drug-coated balloons (DCB) emerged as a “metal-free” alternative delivering an antiproliferative drug to the vessel wall without leaving a permanent implant, thus preserving vessel anatomy, function, and allowing for adaptive remodeling. Currently, DCB are established in percutaneous coronary intervention (PCI) for in-stent restenosis (ISR) and, subsequently, for small-vessel native disease. Their role in larger native coronary arteries, however, remains debated, given the limited evidence from small randomized controlled trials (RCTs) with relatively short follow-up.4

In this context, in a recent paper published in REC: Interventional Cardiology, Sorolla Romero et al. report a timely and rigorous meta-analysis of RCT comparing DCB with DES in patients with native large coronary artery disease (PROSPERO CRD42024602012).5 A total of 2961 patients (n = 1476 for DCB and n = 1485 for DES) from 7 RCT published from 2016 through 2024 were included, and, compared with DES, DCB were associated with a similar risk of the primary endpoint of target lesion revascularization, and all-cause and cardiovascular mortality, myocardial infarction, and major adverse cardiovascular events, but a > 2-fold risk of target vessel revascularization. For angiographic outcomes, although DCB caused less late lumen loss, they were associated with a smaller minimal lumen diameter at follow-up. In light of these results, we hereby hope to provide current and future perspectives on the role of DCB for treatment of native large coronary artery disease.

LESION CHARACTERISTICS

The type of lesions included in the analyzed RCT is a key determinant of the external validity of the study findings, and we outline key considerations below.

• – Across the 7 RCT, patients with high clinical and anatomical complexity were consistently excluded (table 1).6-12 Notably, patients with extensive coronary artery disease (eg, long or multiple lesions, 3-vessel disease, or those requiring multiple devices), severe calcification, left main involvement, or chronic total occlusions were not evaluated. Additional characteristics that appeared among exclusion criteria, and could instead arguably represent favorable scenarios for DCB angioplasty, are requirement for hemodialysis, bifurcations lesions requiring treatment of both branches, and severe coronary artery tortuosity. This selective enrollment underscores the contrast with recent observational studies of DCB use in native large coronary artery disease, which have examined more complex scenarios in which DES may be less effective, technically challenging to deliver, or best avoided to limit long stent segments or multiple overlapping implants (figure 1).13-15

• – The degree of inter-study variability is also of note, particularly given the disproportionate contribution of individual RCT. As appropriately highlighted by the authors, REC-CAGEFREE I⁷ alone accounts for approximately 75% of the total patient population, and leave-one-out analyses yield different results. Moreover, enrollment periods span 8 years (2014–2022), introducing potential variability in procedural techniques, device technology, and adjunctive pharmacotherapy. The observed prediction intervals and measures of heterogeneity further support this consideration.
• – We acknowledge the clinical variability in defining “large” coronary artery disease. This meta-analysis applied a ≥ 2.5 mm-cutoff to define large vessels, which is at the lower end of what many would consider large. In several of the included studies, patients were eligible for enrollment regardless of treated vessel diameter, with some RCT allowing lesions within reference vessel diameters as small as 2.0 mm (table 1). Subgroup analyses within individual studies provide more specific insights into patients treated with larger devices. Given the significant interaction P value in the vessel size subgroup analysis of the largest included RCT,7 it is reasonable to question whether the overall results would have been superimposable had the analysis been limited to larger vessels. These observations should be interpreted in the context of the earlier discussion on the type of lesions included. Finally, this aspect may have sex-specific relevance: although women generally have smaller coronary vessels, a vessel of a given diameter may be more proximal and supply a larger myocardial territory in women than in men, potentially amplifying its clinical significance.16

Table 1. Clinical, angiographic and procedural characteristics excluding patients from each study included in the meta-analysis

Characteristics	Nishiyama et al.6 (CCS) N = 60	REC-CAGEFREE I7 (45%, CCS; 55%, ACS) N = 2271	Yu et al.8 (11%, CCS; 89%, ACS) N = 170	REVELATION9 (STEMI) N = 120	Wang et al.10 (STEMI) N = 184	Gobi´c et al.11 (STEMI) N = 75	Hao et al.12 (STEMI) N = 80
Age, years					> 70		> 80
Hemodialysis	X
Previous MI					X
Previous PCI/CABG						Within 6 months	Within 6 months
Vessel size, mm			< 2.25 or > 4.0		< 2.0 or > 4.0		< 2.5 or > 4.0
Lesion length, mm	≥ 25		> 30
No. of DES or DCB/total DES or DCB length, mm		≥ 3/> 60
Extensive CAD		≥ 3 lesions/vessels				X
Severe calcification or atherectomy	X	X		X			X
Left main coronary artery	X	X
CTO	X	X
Bifurcation requiring treatment in both branches		X
Grafts		X
Severe coronary artery tortuosity						X
ACS, acute coronary syndrome; CABG, coronary artery bypass grafting; CAD, coronary artery disease; CCS, chronic coronary syndrome; CTO, chronic total coronary occlusion; DCB, drug-coated balloon; DES, drug-eluting stent; MI, myocardial infarction; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction.

Figure 1. Patient and lesion factors to be taken into consideration when evaluating native large coronary artery disease for percutaneous coronary intervention. Presence of any one of the factors highlighted beneath DCB should lead the operator to contemplate an approach to limit the number of permanent coronary artery implants. ACS, acute coronary syndrome; CKD, chronic kidney disease; CTO, chronic total coronary occlusion; DCB, drug-coated balloon; DES, drug-eluting stent; DM, diabetes mellitus; HBR, high bleeding risk.

LESION PREPARATION

Lesion preparation is a point of significant heterogeneity among the RCT included in the meta-analysis. For example, the REVELATION trial,9 conducted on patients with ST-segment elevation myocardial infarction, permitted proceeding with DCB angioplasty with a 50% residual percent diameter stenosis after predilation, and thrombectomy if visible thrombus was present, which contrasts with the more commonly embraced ≤ 30% threshold.5 Further complicating the procedural comparison is the timing of patient randomization, as 2 studies randomized patients before assessing the outcome of lesion preparation.10,11 Moreover, the specific methods of lesion preparation varied, with 1 study supporting the use of semicompliant balloon angioplasty before DCB inflation.12 The success of DCB angioplasty depends on a dedicated procedural strategy that hinges on meticulous lesion preparation and careful postoperative assessment, a nuance often lost when comparing outcomes across various methodologies.15,17,18

DCB CHARACTERISTICS

The field is characterized by a diversity of DCB platforms, antiproliferative agents and coatings. While the included RCT largely focus on paclitaxel-coated balloons, a growing body of evidence highlights differences in vascular response, downstream effects, and pharmacokinetics across different DCB, indicating that the choice of drug and coating technology could arguably influence clinical outcomes. Sirolimus-coated balloons have recently shown promising results in various clinical settings. Moving forward, future efforts should continue to differentiate between different technologies, as their clinical performance may not be uniform.19,20 Of note, the balloon coating and mechanism of drug release are also key aspects that should be taken into consideration. The DCB technologies assessed in this meta-analysis all used paclitaxel coating but different in platform; only 3 trials evaluated the same device (DCB; SeQuent Please, B. Braun, Germany) whereas the remaining studies used distinct systems, including an ultrasound-controlled paclitaxel delivery platform.10 Finally, inflation time is important for drug delievery and this was not uniform in the studies included in the meta-analysis, with recommended DCB inflation times as low as 30 seconds.6 Recommendations among studies currently enrolling (MAGICAL SV [NCT06271590] and Prevail Global [NCT06535854]) are also slightly different, and whether this might have clinical implications is still to be elucidated.

ANGIOGRAPHIC AND CLINICAL OUTCOMES

DES implantation typically provides a larger acute gain in lumen diameter than balloon angioplasty, a concept highlighted also within the REVELATION trial,9 where the residual percent diameter stenosis to define a successful procedure was different after DCB angioplasty (< 30%) and DES implantation (< 20%). While the meta-analysis reports the endpoint late lumen loss, we recognize that this metric may not fully capture the relative efficacy of these 2 technologies. The use of endpoints, such as net lumen gain, providing a more comprehensive and meaningful comparison between these 2 fundamentally different strategies by focusing on the overall therapeutic effect on the vessel lumen, rather than just the restenotic response following the intervention, should be implemented in upcoming studies. In addition, we acknowledge the limitation in comparing the incidence rate of composite endpoints such as major adverse cardiovascular events when these include different single components across the studies. Finally, we highlight the importance for future studies to concentrate on the reporting of any target vessel thrombosis, a key safety endpoint which remained underreported in the meta-analysis. Still, a significant concern in clinical practice and a key factor impacting the wider implementation of a DCB-based strategy (COPERNICAN [NCT06353594]).

CONCLUSIONS

The meta-analysis by Sorolla Romero et al. provides a timely summary of the current evidence on the use of DCB in large native coronary arteries, and its findings provide hypothesis-generating evidence that challenges the long-standing paradigm of DES as the default choice for any lesion. This work underscores that the evolution of PCI is ongoing and invites reconsideration of therapeutic algorithms toward a more personalized approach, in which the choice between DCB and DES is guided by patient- and lesion-specific factors (figure 1). Moving forward, the focus must shift towards refining patient selection, optimizing procedural techniques, and conducting further RCT with long-term follow-up to clarify the role of DCB in this new therapeutic paradigm.

FUNDING

None declared.

CONFLICTS OF INTEREST

None declared.

REFERENCES

Over the past decade, the number of patients with severe aortic stenosis treated with transcatheter aortic valve implantation (TAVI) has increased. This rise is attributed to advancements in device technology, which have led to long-term survival comparable to surgical replacement and lower complication rates, including paravalvular leak and need for pacemaker implantation. Consequently, TAVI is now indicated for patients with not only intermediate-to-high risk, but also low risk.1,2

Although pre-TAVI assessment using traditional surgical risk scores, such as EuroSCORE II and STS-PROM, is useful to categorize patients into low, intermediate, or high risk for this procedure, the latest clinical practice guidelines3 recommend a comprehensive assessment, based on clinical and functional measures of the patients, to determine their frailty, and using validated scales to exclude the clinical cardiologist’s subjectivity during consultation.4 This is of paramount importance because frail patients account for 30% of TAVI cases, and it is well known that frailty acts as an independent predictor of mortality and complications after TAVI. However, a patient being categorized as frail does not automatically mean that TAVI will be futile; rather, it indicates that additional measures, beyond alleviating valvular heart disease, should be implemented to improve the patient’s quality of life and survival.5

In an article published in REC: Interventional Cardiology, Bernal- Labrador et al.6 describe the design of a randomized, multicenter clinical trial on the post-TAVI management of patients ≥ 75 years with severe aortic stenosis considered frail (frailty defined as scores < 10 on the SPPB scale and ≥ 3 on the FRAIL scale). The intervention group will receive follow-up video calls made by specialized health care personnel, after discharge and then biweekly, until completing a 90-days follow-up. These telematics visits will address 3 key areas: a) physical exercise (patients and their families will receive instruction on physical activity guidelines tailored to the post-valve replacement recovery period and the older adult’s tolerance); b) nutritional support (oral hypercaloric and hyperproteic supplements will be administered for 3 months after TAVI, to be taken after physical activity); and c) health education (adherence to implemented measures will be assessed weekly, doubts clarified to optimize treatment adherence, and instructions provided on hygienic-dietary measures for better cardiovascular risk factor control). The objective is to determine frailty reversal at 3 months, the rate of readmissions, and the rate of cardiovascular events (nonfatal myocardial infarction, stroke, or need for revascularization), cardiac death, and all-cause mortality at the 3-month and 1-year follow-ups.

This design is novel due to its prospective nature and randomization of patients to the described intervention group or to a control group with follow-up based on the routine clinical practice. As Stamate et al.7 conclude in a literature review, the inclusion of patients in cardiac rehabilitation programs after TAVI is considered safe, even in elderly patients with multiple comorbidities. The studies considered in this review include training programs, patient education, and psychological support, which have been implemented in both hospital and outpatient settings. However, current evidence is limited. Many existing studies have small sample sizes (< 100 patients) and are primarily prospective cohorts. They usually evaluate functional capacity parameters, such as the 6-minute walk test, limb movement improvement, or peak oxygen consumption, rather than hard endpoints such as those assessed by Bernal-Labrador et al.6 An exception is the study by Butter et al.,8 a prospective cohort of more than 1000 patients, which reported a lower 6-month mortality rate in patients involved in cardiac rehabilitation programs after valve replacement.

Protein supplementation as a strategy to improve the physical condition of frail patients has proven effective. However, there is no consensus with clear recommendation guidelines, which do exist in other areas of cardiac rehabilitation, such as heart failure.9 The PERFORM-TAVR10 study, which has already completed its inclusion phase, is the first to assess the synergy of a physical exercise program and external protein intake in frail elderly individuals treated with TAVI to improve frailty indices and quality of life. With a sample size of 200 patients calculated to achieve the primary endpoint of improving physical condition at 3 months, it seems insufficient to answer how to improve hard morbidity and mortality outcomes in this clearly increasing population.

Apart from the physical-nutritional approach to the patient, the study by Bernal-Labrador et al.6 is innovative for resorting to new technologies. The use of telemedicine for monitoring patients with heart disease is limited to experiences of isolated research groups. Yun et al.11 describe a monitoring program for patients with heart failure and varying degrees of frailty, in which telematic monitoring, compared with routine clinical follow-up in outpatient clinics, reduced the hospitalization rate for heart failure decompensation. Telematic monitoring supervised by trained personnel, as proposed in the TELE-FRAIL TAVI trial (NCT06742970),6 allows for addressing alarming signs, optimizing treatment, and educating on hygienic-dietary measures with better results than conventional outpatient visits.

Although in TAVI, telemedicine experience is very limited, it is promising as well. A study by Wong et al.12 that implemented a transitional care program showed that telephone follow-ups 3 days and 30 days after TAVI discharge performed by highly qualified nursing staff effectively identified and managed problems, such as heart failure decompensations, medication titration, and symptoms of anxiety or depression, thus reducing the risk of readmission in frail patients. On the other hand, the study by Herrero-Brocal et al.13 was the first to integrate artificial intelligence into the close monitoring of patients after valve implantation. Compared with the conventional hospitalization group after TAVI (> 48 h), the very early (< 24 h) and early (24-48 h) discharge groups with telematic monitoring did not show statistically significant differences in the primary endpoint (a composite of death, pacemaker implantation, heart failure admission, stroke, myocardial infarction, major vascular complications, or major bleeding 30 days after TAVI). These studies have shown that the addition of new technologies supervised by trained personnel represents an improvement in patient care, as they educate both patients and their families, allow for faster contact in case of doubt, optimizing their care and treatment, decreasing readmission rates, and reducing health care costs.11-13

In conclusion, frailty is a critical factor in the evaluation and management of patients treated with TAVI. Interventions targeting frailty, such as exercise and nutrition programs, show promising results for improving postoperative outcomes. The implementation of new technologies to optimize pharmacological treatment, alleviate anxiety, and adapt lifestyle is mandatory to improve the long-term outcomes of these patients, beyond any advances made in the implantation technique.

FUNDING

None declared.

CONFLICTS OF INTEREST

None declared.

REFERENCES

Over the past 5 years, tricuspid valve has decisively entered the interventional spotlight. Driven by the growing recognition of the morbidity and mortality associated with tricuspid regurgitation (TR) across all severity grades, coupled with the limitations of both surgical and medical management, the field has been actively exploring less invasive, catheter-based solutions. To date, 2 transcatheter tricuspid valve edge-to-edge repair systems (PASCAL, Edwards Lifesciences, United States, and TriClip, Abbott, United States), have received both the CE mark and the approval from the U.S. Food and Drug Administration (FDA) for the treatment of patients with severe, symptomatic TR. Meanwhile, the TricValve system (P&F Products & Features, Austria), remains as the only CE-and FDA-approved transcatheter heterotopic device.

Despite recent advances, improvements in all-cause mortality and heart failure-related hospitalization have not been consistently demonstrated. Instead, the clearest benefit of transcatheter tricuspid procedures has been amelioration of health status and functional class. This has driven a paradigm shift in therapeutic goals from classic endpoints such as survival to a more patient-centered focus on quality-of-life metrics and patient-reported outcomes. One potential explanation for the limited impact on mortality is that current repair-based transcatheter therapies often leave behind residual TR. Persistent moderate or greater TR has been associated with worse clinical outcomes,1 underscoring the need for more definitive solutions.

Transcatheter tricuspid valve replacement (TTVR) has the potential to completely abolish TR, representing a promising alternative for patients with complex anatomies unsuitable for edge-to-edge repair, including patients with baseline massive or torrential TR, severe leaflet tethering, large coaptation gaps or pacemaker-induced leaflet impingement. Among available TTVR devices,2 the EVOQUE system (Edwards Lifesciences, United States) became the world’s first dedicated transcatheter valve replacement device to receive regulatory approval (CE mark in 2023) for broader commercial use beyond clinical trials. The EVOQUE system features a self-expanding nitinol frame with bovine pericardial leaflets and an intra-annular sealing skirt, which is delivered through a 28-Fr transfemoral system with 3 planes of motion for precise positioning. The valve has a unique mechanism that uses the annulus, leaflets, and chords for stable, non-traumatic fixation through 9 ventricular anchors. It is currently available in 4 sizes (44 mm, 48 mm, 52 mm, and 56 mm) covering annular diameters from 37 mm to 58 mm and perimeters of up to 169 mm.

Two pivotal trials have demonstrated the technical feasibility and safety of the EVOQUE system, with substantial TR reduction and favorable short-term clinical outcomes as a standalone therapy (TRISCEND) or in combination with optimal medical therapy (TRISCEND II).3 However, randomized clinical trials are not always representative of real-world practice. Observational data from non-trial settings are, therefore, essential to complement and contextualize findings from randomized clinical trials.

In a recent article published in REC: Interventional Cardiology, Pardo Sanz et al.4 share their experience with the orthotopic EVOQUE valve implantation in a series of 10 consecutive patients, with outcomes assessed at 30 days. The mean age of the population (77 years) with high prevalence of comorbidities (including atrial fibrillation and 40% pacemaker prevalence) and symptom burden (all had New York Heart Association [NYHA] class ≥ 2 or recurrent hospitalizations) illustrate the frail and complex nature of this population, which mirrors that of the TRISCEND II trial and followed similar exclusion criteria (severely depressed right ventricular [RV] systolic function, unsuitable anatomies, life expectancy < 12 months). All patients had been considered ineligible for repair-based therapies due to complex tricuspid anatomy. Just a few years ago, these patients were often considered to have no treatment options.

The authors reported a 100% procedural success rate, a median procedural time of approximately 2 hours, consistent reduction of TR to mild or less in all cases, absence of major paravalvular leaks, and no in-hospital mortality. These results are highly encouraging and confirm the technical reproducibility of the EVOQUE system across centers and operators outside high-volume trial sites. Still, this procedure is resource-intensive, logistically complex, and requires multidisciplinary coordination, advanced peri-procedural imaging and available backup for cardiac surgery and emergent pacemaker implantation capabilities. In this series, 2 patients experienced transient RV failure, a severe complication. Abrupt elimination of torrential TR unequivocally leads to an acute rise in RV afterload. The RV, adapted to unloading into a low-pressure circuit, must suddenly adapt to a now-competent valve, an adjustment that some ventricles, particularly those with borderline or “pseudo-normalized” function, may not tolerate acutely. This scenario is similar to the afterload mismatch phenomenon in left-sided valve interventions. Additionally, one must consider the mechanical interaction between the prosthetic valve and the RV natural motion, which may further impair longitudinal function, the main determinant of RV systolic performance. Although managed successfully with inotropic support, these cases underscore the need for an exquisite RV assessment during pre-procedural planning. Future studies may benefit from integrating hemodynamic, load-independent data derived from pressure-volume loops along with multimodality imaging to more accurately characterize the RV and identify patients at risk of post-procedural decompensation.

Another relevant concern after TTVR is the risk of conduction disturbances.2 One patient developed complete atrioventricular block, requiring permanent pacing. This was a patient with pre-existing right bundle branch block, a known predictor for the need of pacemaker implantation in other percutaneous transcatheter valve therapies. The anatomic proximity of the EVOQUE anchors to the conduction system, coupled with baseline conduction abnormalities, likely triggered this outcome. Optimal pacing strategies post-TTVR remain undefined, whether via transvalvular leads, coronary sinus pacing, leadless systems, or surgical epicardial leads. While technical refinements may eventually mitigate this risk, for now, comprehensive pre-implantation rhythm evaluation and prolonged postoperative telemetry monitoring are recommended.

Two patients were diagnosed with prosthetic valve thrombosis at the 1-month follow-up computed tomography despite adequate anticoagulation. Neither had symptoms or elevated transprosthetic gradients, raising, perhaps, the differential diagnosis of hypoattenuated leaflet thickening. This subclinical phenomenon has already been reported in up to 32% of cases in contemporary series.5 Since transvalvular gradients remained low, it is unclear whether these subclinical thrombi would impact long-term valve durability or lead to embolic events. Nonetheless, the implications are significant. Should routine post-procedural computed tomography be performed? And what is the optimal antithrombotic regimen? In TRISCEND trials, oral anticoagulation (aiming International Normalized Ratio [INR] of 2.5-3.5) with adjuvant aspirin was recommend to all patients for the initial 6 months. This intensive antithrombotic regime may have explained, in part, the notable rate of severe bleeding events registered.3 In contrast, the present cohort remained on previous anticoagulation strategies without antiplatelet therapy. As with transcatheter aortic valve replacement, we may need to rethink antithrombotic protocols specifically for the low-flow, low-pressure tricuspid bioprostheses —potentially balancing bleeding risks in an elderly population with thrombotic complications that may go unnoticed without advanced imaging.

Finally, a rare but instructive complication was reported, a case of severe functional mitral regurgitation occurring 5 days after the EVOQUE valve implantation, which resolved with diuretic and inodilator therapy. The mechanism may relate to the acute preload normalization after TR elimination and increase in forward stroke volume, which unmasked or exacerbated the preexisting mitral regurgitation.6 Once again, intra and postoperative re-evaluation of coexisting valvular lesions is mandatory.

While the technical success and hemodynamic outcomes are commendable, the absence of formal assessment of quality-of-life and patient-reported outcomes is a limitation. In the TRISCEND II trial, improvements in Kansas City Cardiomyopathy Questionnaire (KCCQ) scores and NYHA class were key indicators of clinical benefit. Even when hard endpoints remain unchanged, post-procedure functional improvement (symptoms, activities of daily living, and independence) stands as a critical measure of clinical value, particularly in a patient population where survival may not reflect therapeutic success.

As TTVR moves from innovation to integration, 3 priorities emerge:

1. Long-term durability. What will the 5- and 10-year performance of the EVOQUE valve look like in terms of structural integrity, thrombotic risk, and reintervention rates?
2. Patient selection. Can we identify robust predictors (clinical, imaging or biomarker-based) to guide the choice between tricuspid valve repair and replacement?
3. Broader applicability. A 17% treatment rejection rate based on feasibility assessments was reported in the study, implying that there are still patients who are ineligible for this therapy. In fact, a 74% screening failure rate was documented in the first real-world TTVR registry.7 Besides, should we scale this therapy beyond high-volume centers?

The tricuspid landscape is evolving rapidly. The study by Pardo Sanz et al.4 exemplifies what is achievable when technological innovation meets clinical pragmatism. The EVOQUE valve stands at the frontier of transcatheter therapy, offering a lifeline to patients who previously had none. Yet, success demands meticulous patient selection, expert execution, and extended surveillance to guarantee long-term results. As we refine the art and science of tricuspid interventions, real-world experiences such as this one will remain essential to optimizing clinical practice and extending the evidence of novel transcatheter therapies.

FUNDING

C. Herrera is a beneficiary of a Río Hortega grant from Instituto de Salud Carlos III (CM23/00238, MV24/00095).

CONFLICTS OF INTEREST

None declared.

REFERENCES