The future of interventional cardiology

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

Transcatheter aortic valve implantation (TAVI) has revolutionized the treatment of aortic stenosis and is currently the treatment of choice for degenerative aortic stenosis from 75 years of age. Despite its minimally invasive nature, for years, the length of stay after TAVI was approximately 1 week.1 Due to technological advancements and perioperative care, in recent years, there has been a progressive reduction in the length of stay after TAVI. Several factors have contributed to this trend, such as patient selection (preoperative planning and inclusion of patients of lower surgical risk), simplification of the procedure (use of local anesthesia, secondary radial access, smaller caliber catheters and vascular complications, standardization of implantation techniques with fewer conduction disorders) and optimization of peri- and postoperative care (accelerated circuits following after TAVI and outpatient monitoring).

In an article published in REC: Interventional Cardiology, Pimienta González et al.2 present the results of the first 100 patients treated with TAVI in a noncardiac surgery center, with the implementation of an early discharge protocol since the beginning of the program. The patients’ mean age was 82 years and their surgical risk was low-to-intermediate (Society of Thoracic Surgeons score of 4.38%). A total of 97% of all procedures were performed via transfemoral access (95% via transcatheter access) and 3% via surgical transaxillary access, in patients with mostly native aortic stenosis (98%). All patients received a self-expanding supra-annular valve: 87% an Evolut valve (Medtronic, United States) and 13% an ACURATE valve (Boston Scientific, United States). There were no deaths during the procedure nor any cases of conversion to open surgery. The median length of stay was 2 days (1-19), with 76% of patients being discharged within the first 48 hours. The 30-day event rate was low: pacemaker, 13%; major vascular complication, 4%; stroke, 1%; and cardiovascular mortality, 1%. There were only 6% readmissions within the first month.

Procedural results and the subsequent care are remarkable, considering an early discharge protocol in an unselected population in a center without prior experience performing TAVI. A quarter of the procedures were proctored, which undoubtedly contributed to the excellent results reported. A total of 27% of patients were discharged at 24 hours and 76% at 48 hours due to a rigorous peri-TAVI care protocol consisting of in-person visit 1 week prior to the procedure, nursing call 48 hours prior to the procedure, telephone consultation 48 hours following discharge and in-person consultation at 10 days, and the systematization of the conduction disorders approach, which is currently the “Achilles’ heel” of TAVI and the main reason for delayed discharge.

However, there are some limitations that should be mentioned. Firstly, the authors do not specify which clinical criteria were predefined to categorize hospital discharges as very early (< 24 h), early (24-48 h) or late discharges (> 48 h), nor the percentage of patients who received ambulatory electrocardiographic monitoring; information that could be useful for other centers with similar characteristics. Furthermore, all procedures were performed under general anesthesia, which contrasts with most protocols of early discharge, which prioritize local anesthesia and conscious sedation, given its potential benefit in terms of mortality, speed of recovery and shorter length of stay.3 Finally, one cannot rule out some selection bias (low surgical risk; 3, alternative access; 3%, bicuspid valves; 2%, valve-in-valve; 0%, pure aortic regurgitation). Nevertheless, the work of Pimienta González et al.2 exemplifies the possibility of implementing this type of protocols (duly prespecified and proctored) during the learning curve in contemporary clinical practice.

The growing number of TAVIs has triggered the development of standardized measures and protocols aimed at reducing the length of stay and improving the efficiency of resources. Several studies have demonstrated the safety and efficacy profile of an early discharge strategy (24-72 h) after TAVI. In 2015, Durand et al.4 first described early discharge within the first 72 hours in selected patients treated with transfemoral TAVI with local anesthesia as a safe strategy with a low rate of complication. Subsequently, large-scale international studies reaffirmed the safety profile of an early discharge strategy through the implementation of dedicated protocols with rapid recovery circuits and pre-established criteria for early discharge.5-8 The Vancouver 3M Clinical Pathway study, with more than 400 patients from 13 North American low- (< 100 TAVIs per year), intermediate- or high-volume centers (> 200 TAVIs per year) achieved hospital discharges within 24 hours in 80% of patients and within 48 hours in 90%, regardless of the experience and volume of the participant centers.6 This circuit was subsequently validated in a low-volume center with limited experience performing TAVIs, with a mortality rate of 0.6% and a readmission rate of 6.7% at 30 days;9 figures very similar to those reported by Pimienta González et al.2 in their series. However, these findings contrast with data from large registries that demonstrated that there is an inverse association between volume and mortality, especially for the first 100 cases.10 While the results of the present study suggest a possible attenuation of the learning curve with new devices and contemporary implantation techniques, they highlight the importance of optimizing and systematizing not only the aspects of the procedure (“minimalist TAVI”), but also the clinical and logistical aspects throughout the entire care process, from before to after the procedure.

Of note, most of the evidence on early discharge after TAVI comes from studies with a predominance of balloon-expandable valves (traditionally associated with lower rates of pacemakers), which contrasts with the present work, in which 100% of the devices used were self-expanding valves. Some studies have previously explored the safety profile of early discharges in patients treated with self-expanding valves. In an American registry with nearly 30,000 patients who underwent elective TAVI with the self-expanding Evolut valve, the discharge rate the next day after TAVI was close to 60%.11 Similarly, Ordoñez et al.12 described the safety profile of early discharge after TAVI with the self-expanding ACURATE neo valve in 368 unselected patients, 55% at 24 hours and 74% at 48 hours, without observing an increased risk of death or readmission at 30 days.

In conclusion, the study by Pimienta González et al.2 is yet another demonstration of the applicability of this type of clinical pathways in our environment and the routine clinical practice, provided they are conducted in a structured and systematized manner.13-15 After the simplification of the procedure, the latest generation devices, contemporary implantation techniques, the patients’ lower risk profile and postoperative expansion of accelerated circuits, the “minimalist” hospitalization after “minimalist TAVI” has already become a common practice and a key tool in terms of efficiency to be able to face the increasing number of TAVIs in the coming years and the expansion of its indications.

FUNDING

None declared.

CONFLICTS OF INTEREST

None declared.

REFERENCES

Atrial fibrillation (AF) is a common arrhythmia with an incidence rate of approximately 2% of the general population in the developed world. It is usually a consequence of underlying cardiovascular or thoracic morbidities, cardiovascular stress, toxicities, or age-related degeneration. The presence of AF may provoke or aggravate cardiocerebrovascular disease, resulting in stroke, dementia, worsening heart failure, disturbances of mood and quality of life. Thromboprophylaxis is a fundamental and critical element of its management.

Warfarin, the most widely used oral vitamin K antagonist (VKA), was first used clinically during the 1950s but its application for stroke prevention in patients at risk of AF-related thromboembolism only became clinically commonplace after the metanalysis of early trials vs placebo, or the then standard of care. This showed a remarkable stroke reduction of 64% and an often forgotten 26% reduction of mortality, which favored anticoagulation.1 There is, however, one major problem: major bleeds are common (2%-3% per year), of which intracranial bleeding (1% per year) often causes more serious strokes than those of ischaemic etiology. Major haemorrhage is usually due to an underlying arteriopathy and/or excessive anticoagulation due to drug-drug and food-drug interactions increasing the anticoagulant potency of the VKA. Regular monitoring of the anticoagulation status is necessary, and patient education/counselling is needed to encourage patient adherence and persistence with therapy. Both patients and doctors often prefer to use the considerably less effective approach using aspirin, despite its associated bleeding risks.

Direct oral anticoagulants (DOACs), which are at least equally effective and less complicated by intracranial bleeds, entered the therapeutic armamentarium in 2010.2 Dosing depends to a certain degree on a few patient characteristics, such as renal function, age and body weight. They are not compromised by food-drug interactions but co-medication with P-glycoprotein inhibitors does result in elevated plasma concentrations. DOACs do not need regular monitoring. As a class effect, the risk of major gastrointestinal bleeding is 25% higher, and clinically relevant non-major bleeding remains a frequent and troublesome concern. It does not come as a surprise, then, that many patients continue to be reluctant to accept anticoagulant therapy to avert a future, albeit serious event. Drug doses are often skipped, and discontinuation is a common finding.3

Some patients are at high risk of bleeding complications, regardless of which anticoagulant is being used, and others remain vulnerable to ischaemic stroke, even when the anticoagulant is properly prescribed and appropriately taken. Since most AF-related thrombi form in the left atrial appendage (LAA) a mechanical approach, such as excising, closing or occluding the appendage is a therapeutic option. When patients with high-stroke-risk AF undergo cardiac surgery, many surgeons routinely excise the LAA as a preventive measure. For other patients the LAA may be closed with a ligature inserted transcutaneously. However, for most patients at high risk of AF-related stroke for whom a mechanical solution is thought necessary, an occlusion device may be inserted transvenously and placed through the atrial septum and into the LAA. Following device insertion, antiplatelet drugs or full or reduced-dose anticoagulants are used to prevent thrombus formation on the newly implanted foreign body. Although the therapy has proven to be as effective as VKA anticoagulation4 and is possibly, at least, as effective as DOAC therapy,5 this remains to be conclusively proven by randomized clinical trials.

The Left Atrial Appendage Occlusion Study (LAAOS III) has conclusively demonstrated that removing/ligating the orifice of the LAA is very effective at reducing stoke or systemic embolism in patients with high-risk AF who undergo surgery for coronary revascularization or heart valve surgery.6 However, almost 80% of the patients from the study were also still on anticoagulants 3 years after surgery, which raises the question about whether the most effective stroke-reducing therapy for patients with high-risk AF, not undergoing surgery, should also be a combination of oral anticoagulation and LAAC (left atrial appendage closure) with a mechanical device. It does not come as a surprise that a new study (LAAOS IV) recruiting AF patients at high risk of stroke despite anticoagulation (CHA₂DS₂-VASc score ≥ 4) will compare anticoagulation with anticoagulation plus a mechanical device.7 (LAAOS IV - Research Studies - PHRI - Population Health Research Institute of Canada).

In a recent paper published in REC: Interventional Cardiology, Amaro et al. described their study which is also designed to address this issue, choosing a specific group of patients who have suffered a stroke despite anticoagulation (breakthrough stroke).8 Although this is not a rare event with an incidence rate is 1%/year in anticoagulated patients due to AF, there is no accepted and fully investigated therapeutic solution to this clinical problem (figure 1). If the stroke is ischaemic and cardioembolic it is likely related directly to the AF (3 of 4 breakthrough strokes). Anticoagulant therapy might not have been prescribed or taken correctly, which can be improved. If current antithrombotic therapy seems optimal, as in the proposed study by Amaro et al.8, physicians sometimes consider changing the anticoagulant, increasing VKA to an INR > 3.0, using an off-label high dose of a DOAC, or adding antiplatelet therapy like aspirin—none of which appear beneficial. In these circumstances, a practical solution may be switching to a mechanical device requiring a short course of antiplatelet therapy or low-dose anticoagulation, or adding a mechanical device to the existing anticoagulant regimen. Although none of these approaches has been fully demonstrated, substantial observational data 9-11 support transitioning from anticoagulation to LAAC therapy, justifying ongoing randomized clinical trials in this patient population. These trials compare LAAC therapy to anticoagulant treatment, or to no thromboprophylaxis if patients with bleeding complications associated with oral anticoagulants are also elilgible for enrollment. The results of the OCCLUSION-AF PROBE design trial, with 750 patients and documented AF and ischaemic strokes or transient ischaemic attacks randomized to DOAC or LAAC are expected shortly.12

Figure 1. Approach to patients with atrial fibrillation who suffer a stroke whilst treated with an anticoagulant. AF, atrial fibrillation; D/D, drug-drug; F/D, food-drug; LAAC, left atrial appendage closure; LAAO, left atrial appendage occlusion; OAC, oral anticoagulants. ^a Direct oral anticoagulants drug level/coagulation tests of limited value with short acting medications. ^b Plus short term OACs, longer term aspirin or dual antiplatelet therapy, or low dose of direct oral anticoagulants.

There is some observational study support for the hybrid approach of adding LAAC to inadequate anticoagulant therapy, a strategy for preventing a recurrence of oral anticoagulation-resistant cardioembolic stroke in patients with AF and no major oral anticoagulation-related bleeding complications.13 Several groups have proposed and are conducting such studies, such as the ELAPSE trial (Early closure of left atrial appendage for patients with atrial fibrillation and ischaemic stroke despite anticoagulation therapy; NCT05976685) which will help them, together with the ADD-LAAO study (Oral anticoagulation alone vs oral anticoagulation plus left atrial appendage occlusion in patients with stroke despite ongoing anticoagulation) led by Amaro et al. to confirm or refute the value of this hybrid approach. Successful results of these studies would help us widen extensively the indication for LAAC therapy, which is now a procedure that can be performed by skilled operators with a complication rate no greater than that of other common procedures in interventional cardiology.14

This strategy of using all antithrombotic approaches may be more effective therapy for patients resistant to just one strategy.

FUNDING

None declared.

CONFLICTS OF INTEREST

A.J. Camm has received personal fees from Acesion, Anthos, Incarda, Milestone, Abbott, Boston Scientific and Johnson and Johnson.

REFERENCES