Weekly Journal Scan: transcatheter vs. surgical treatment of combined severe aortic valve stenosis and obstructive coronary artery disease

This comment refers to ‘TransCatheter aortic valve implantation and fractional flow reserve-guided percutaneous coronary intervention versus conventional surgical aortic valve replacement and coronary bypass grafting for treatment of patients with aortic valve stenosis and complex or multivessel coronary disease (TCW): an international, multicentre, prospective, open-label, non-inferiority, randomised controlled trial’, which was published in The Lancet. https://doi.org/10.1016/S0140-6736(24)02100-7. The TransCatheter Valve and Vessels Trial (TCW) trial was an international, multicentre, industry-funded, open-label, randomized clinical trial (RCT) aiming to test the non-inferiority of transcatheter aortic valve implantation (TAVI) plus fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) as compared with surgical aortic valve replacement (SAVR) plus coronary artery bypass grafting (CABG) in patients with severe aortic stenosis (AS) and concomitant obstructive coronary artery disease (CAD).1 Patients 70 years of age or older with symptomatic severe AS (defined according to current guidelines)2 and concomitant multivessel or complex CAD, which had been deemed feasible for both transcatheter and surgical treatment by the local heart team, were enrolled. Complex CAD was defined as the presence of at least two de novo coronary lesions (≥50% diameter stenosis on visual estimation) in any native epicardial coronary artery or large side branches (calibre > 2 mm) or a single left anterior descending (LAD) lesion (>20 mm length) involving a bifurcation with a diagonal branch. In the FFR-guided PCI plus TAVI group, lesions with an FFR of 0.80 or less were treated with drug-eluting stent implantation. Transcatheter aortic valve implantation could be performed either during the same procedure or as a staged procedure within 40 days from index PCI, using a self-expanding valve (CoreValve Evolut R or Evolut PRO, Medtronic). In the SAVR plus CABG group, FFR guidance was not mandatory, but left to the surgeon's discretion. Patients received CABG (with a strong recommendation for the use of arterial grafts) plus SAVR with a bioprosthetic aortic valve. The primary endpoint was a composite endpoint of all-cause death, myocardial infarction (MI), disabling stroke, clinically driven target-vessel revascularization, valve reintervention, and life-threatening or disabling bleeding at 1 year. Major secondary endpoints were major adverse cardiovascular events, defined as a composite of cardiovascular death, all stroke, MI, unscheduled coronary events, or valve reintervention at 1 year and a composite of all-cause death and stroke at 1 year. Between May 2018 and June 2023, a total of 172 patients (mean age, 77 years; 31% female) were enrolled at 18 tertiary medical centres across Europe, of whom 91 were assigned to the FFR-guided PCI plus TAVI group and 81 to the SAVR plus CABG group. The mean EuroSCORE II was 2.5%, and the mean Society of Thoracic Surgeons-Predicted Risk of Mortality score was 2.4%, corresponding to a low-risk population. Mean SYNTAX score was 12, and multivessel CAD was present in 76% of patients. A sample size of 320 patients was calculated to provide the study with 90% power to demonstrate non-inferiority of PCI plus TAVI vs. SAVR plus CABG, assuming a primary endpoint rate of 30% in the SAVR plus CABG group and a non-inferiority margin of 15%. The trial was stopped prematurely due to a significant between-group difference in the incidence of the primary endpoint and all-cause death. Therefore, 172 patients were recruited in total and were followed up at 1 year. At 1 year, the incidence of the primary endpoint was 4% in the FFR-guided PCI plus TAVI group and 23% in the SAVR plus CABG group [risk difference, −18.5%; 90% confidence interval (CI), −27.8 to −9.7; P for non-inferiority < 0.001). Fractional flow reserve-guided PCI plus TAVI was found to be superior to SAVR plus CABG [hazard ratio (HR), 0.17; 95% CI, 0.06–0.51; P for superiority < 0.001], entirely driven by a reduction in all-cause death [none (0%) of 91 patients vs. seven (10%) of 77 patients] and life-threatening or disabling bleeding [two (2%) vs. nine (12%); HR, 0.17; 95% CI, 0.04–0.80]. Major adverse cardiovascular event rate at 1 year was lower in the FFR-guided PCI plus TAVI group than in the SAVR plus CABG group (3% vs. 14%), while the incidence of atrial fibrillation was higher in the latter than in the former (14% vs. 4%), and the rate of pacemaker implantation was lower (3% vs. 10%). Over the past two decades, a growing body of evidence from RCTs comparing TAVI vs. SAVR laid the foundations for a paradigm shift in the therapeutic approach to symptomatic severe AS.3 Transcatheter aortic valve implantation has become the recommended treatment for patients at high risk for conventional surgery, and the results of trials in patients at intermediate or low surgical risk have progressively extended the indication of the transcatheter approach across the whole spectrum of predicted surgical risk.2,3 Yet, most of these trials excluded patients requiring revascularization, although significant CAD is a frequent comorbidity in patients with severe AS that confers higher risk of clinical events.4 Current European Society of Cardiology guidelines indicate the presence of significant multivessel CAD requiring surgical revascularization as one of the anatomical factors in favour of a surgical treatment.2 Yet, either simultaneous SAVR and CABG or late SAVR after CABG carry a higher procedural risk than isolated SAVR.5 Following the favourable outcomes of isolated TAVI, a combined transcatheter approach of TAVI and PCI has become attractive.6 The recent NOTION-3 trial has shown the superiority of an FFR-guided PCI over a conservative treatment strategy in patients undergoing TAVI with respect to a composite endpoint of all-cause death, MI, or urgent revascularization at 2 years.7 However, a combined surgical arm was not part of the comparison. A sub-analysis of the SURTAVI trial showed no significant difference in the incidence of all-cause death or stroke at 2 years between TAVI plus PCI and SAVR plus CABG in patients with severe AS and non-complex CAD.8 Yet, this trial was not designed for this purpose, and myocardial revascularization was not guided by an invasive functional assessment of lesion severity. The TCW trial is the first RCT to provide a direct comparison of transcatheter vs. surgical treatment of combined symptomatic severe AS and obstructive CAD. Unfortunately, the trial was interrupted prematurely in the face of an apparent imbalance in the number of deaths and primary endpoint events in the surgical arm as compared with the transcatheter arm. This was mainly related to the very low event rates observed in the PCI plus TAVI group, while the observed rate of the primary endpoint at 1 year in the SAVR plus CABG group (23%) was lower than assumed for sample size calculation (30%). These and other statistical considerations, including the generous non-inferiority margin (15%) and the high cross-over rate (11%) from the surgical to the transcatheter group should be considered when interpreting the results of the TCW trial, which was largely underpowered to test the original hypothesis. The positive outcomes of FFR-guided PCI plus TAVI compared with SAVR plus CABG, confirmed by additional per-protocol and as-treated analyses, were already evident at 30 days, as shown by the early separation of Kaplan–Meier curves, and progressively attenuated during further follow-up. This is not unexpected, as less invasive treatments typically perform better in the early phase due to lower procedural complication rates, while the impact of surgery on clinical outcomes usually consolidates over time. For this reason, a longer follow-up is needed to confirm these findings. The inclusion of patients for whom both PCI plus TAVI and SAVR plus CABG had been deemed feasible by the local heart team may have introduced selection bias. Furthermore, CAD complexity was relatively low in the TCW trial, as demonstrated by the small proportion of patients with three-vessel CAD (24%) and left main stenosis (3%), as well as the low median SYNTAX score (12% in the overall population). These findings underscore the importance of an accurate patient selection, as patients with low anatomical complexity might be exposed to an unjustified higher surgical risk. Interestingly, more than 20% of patients in the SAVR plus CABG group lacked a stenosis on LAD (i.e. the prognostically relevant target vessel for CABG), and 36% received an incomplete revascularization (as compared with 19% in the FFR-PCI plus TAVI group), which might have contributed to the worse outcome observed in the surgical arm. An important methodological feature of the TCW trial was the extensive use of invasive functional assessment (i.e. FFR) to guide PCI. The left ventricular pressure overload determined by AS, leading to ventricular remodelling and hypertrophy as well as to increased intracavity pressure, may have an impact on hyperaemic physiological indices like FFR, potentially leading to an underestimation of the functional severity of a stenosis.9 This is particularly relevant when PCI is performed before treatment of severe AS.4 The positive results of this1 and other recent RCTs7 provide further support to the value of invasive functional assessment to guide PCI in patients undergoing TAVI. In contrast, the low use (30%) of FFR in the SAVR plus CABG group was a drawback of the trial, which might have influenced the results. The design of the TCW trial did not allow addressing the still open question regarding the best timing of PCI with respect to TAVI, as TAVI was systematically performed after PCI (either during the same procedure or as a staged procedure within 40 days). Percutaneous coronary intervention timing in patients undergoing TAVI should consider a number of factors, including clinical presentation, CAD complexity, the extent of myocardium at risk, bleeding risk, and the type of transcatheter heart valve.4 Performing PCI after TAVI introduces the potential issue of challenging coronary artery re-access, particularly when implanting self-expanding valves with supra-annular leaflet position like in the TCW trial. As such, the observed findings cannot be extrapolated to other transcatheter heart valves. The inclusion of older patients (median age, 77 years), the net preponderance of White patients (90%), and low representation of female sex (∼30%) represent additional limits to the generalizability of the results. These considerations are essential with a view to a lifetime management of patients with severe AS and concomitant CAD,10 a perspective that should take into account a number of additional issues, including valve durability, re-intervention, and risk of permanent pacemaker implantation.11 In conclusion, the TCW trial shows that, in a small population predominantly represented by low surgical risk patients with severe AS and concomitant CAD with low anatomical complexity, a transcatheter strategy of FFR-guided PCI plus TAVI can be safely performed with favourable short-term clinical outcomes, potentially representing a valuable treatment option for these patients. Larger trials with longer follow-up are needed to confirm these promising findings and to determine whether this clinical benefit extends to a population of patients with higher CAD complexity. R.V. is a consultant for Abbott Vascular and Medtronic; received lecturing fees from Abbott Vascular, Abiomed, Daiichi Sankyo, Edwards Lifesciences, Medtronic, Novartis, and Philips; and served as a member of advisory boards for Amarin and Amgen. D.P. received lecturing fees from Daiichi Sankyo, outside the submitted work.