SOURCE 3 at 1 year: what can we learn?

This editorial refers to ‘SOURCE 3: 1-year outcomes post-transcatheter aortic valve implantation using the latest generation of the balloon-expandable transcatheter heart valve’†, by O. Wendler et al., on page 2717. The SAPIEN 3 valve is the latest generation of balloon-expandable transcatheter heart valve (THV). Currently, transcatheter aortic valve implantation (TAVI) is more often performed with this valve than with any other. The first-in-human experience with this device began >5 years ago. There were no procedural deaths or major complications, albeit in a small number of transfemoral patients (just 15).1 The subsequent SAPIEN 3 EU trial expanded this experience to 150 patients in Europe and Canada.2 All-cause mortality at 30 days was somewhat higher (5.3%), largely attributable to high-risk patients undergoing alternative access who had a 30-day mortality of 11.1%. In contrast, the 64% of patients who had a transfemoral procedure had a very low 30-day mortality of 2.1% and a 1-year mortality of 8.4%, the lowest reported 1-year mortality in a large centrally adjudicated registry.2 , 3 The mortality in intermediate-risk transfemoral patients of just 1.0% at 30 days and 7.9% at 1 year was impressively low at the time. The SOURCE 3 (SAPIEN 3 Aortic Bioprosthesis European Outcome) registry with 1946 patients from 80 European centres in 10 countries is the largest published experience with this device to date.4 What can we learn from this very large ‘real-world’ post-approval multicentre registry? Reassuringly, all-cause mortality in SOURCE 3 was comparable not only with the earlier SAPEN 3 EU trial, but also with the large US pre-approval PARTNER 2 trials.5–7 Mortality at 30 days was 2.2% and at 1 year was 12.6%. As expected, the post-approval mortality rates lie between the as-treated mortality rates seen in the 1078 patient intermediate-risk and 583 patient high-risk PARTNER 2 SAPIEN 3 trials both at 30 days (1.1% and 2.2%) and at 1 year (7.4% and 14.4%). In the European clinical setting, 1-year all-cause mortality has continued to fall: from 23.9% in the SOURCE registry with the SAPIEN valve, to 19.4% in the SOURCE XT registry with the SAPIEN XT valve, and now to 12.6% in SOURCE 3 (Figure 1).4 , 8–11 In part, this appears to be the result of improvements in the valve and its delivery system. However, as the authors note, this is also due to inclusion of lower risk patients, improvements in patient selection, and improvements in techniques.4 One-year all-cause mortality in SAPIEN valve registries. The SOURCE 3 registry is highlighted. *To allow comparison between registries, where possible trial outcomes are reported as-treated. The SOURCE 3 registry documents that in European clinical practice transfemoral access is increasingly preferred, being utilized in 87.1% of patients. In contrast, alternative access has continued to decline, accounting for only 12.9% of procedures (apical 72%, aortic 21%, subclavian 2%, carotid 5%). Although evidence for TAVI in intermediate-risk patients mounts, most patients continued to be elderly (mean age 81.6 years) and have co-morbidities (mean logistic EuroSCORE I 18.3%).4 , 6 As is generally the case, mortality was lower with the transfemoral arterial approach than with alternative access routes. This was reflected in lower 1-year mortality rates in the SOURCE 3 registry (transfemoral 11.8% vs. alternative access 18.5%).4 Comparisons between transfemoral and non-transfemoral access outcomes are problematic, largely due to selection bias. However, the corollary is that favourable outcomes with transfemoral TAVI cannot necessarily be extrapolated to alternative access TAVI. Unfortunately we have little evidence with which to compare various alternative access TAVI options directly with open heart surgery. In SOURCE 3, the 30-day rate of new pacemaker implantation was 12.1%, similar to the rates seen in the PARTNER intermediate-risk and high-risk trials (10.2% and 13.3%, respectively).4 , 7 Reassuringly, only 1.1% of patients required a new pacemaker between 30 days and 1 year, similar to the 2.2% and 3.5% seen in the PARTNER 2 trials.5 , 6 There was no evidence of a ‘catch-up’ in terms of late pacemakers in comparison with other valves commonly associated with higher 30-day pacemaker rates. Importantly, clinically important paravalvular aortic regurgitation was rare in the SOURCE 3 registry.4 At 1 year, moderate or greater regurgitation was reported in only 2.6% of patients, similar to the 2.6% and 1.5% rates reported in the PARTNER 2 high- and intermediate-risk trials.5 , 6 In fact, no patient in the SOURCE 3 registry had severe regurgitation at 1-year follow-up. As a consequence, aortic regurgitation did not appear to be a predictor of mortality in multivariate analysis, a major shift from earlier studies where this was seen to be a major disadvantage of TAVI. Real-world clinical post-approval experience is reassuringly consistent with the pre-approval trials. Favourable outcomes at 1 month previously reported translate into favourable outcomes at 1 year. TAVI can be a relatively reproducible and reliable therapy. Future trials may well prove TAVI to be the default therapy for the majority of patients with aortic stenosis. Conflict of interest: J.G.W. is a consultant to Edwards Lifesciences. A.A.-T. has no conflicts to declare.

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