Dr. Ayşe Nur Özkaya İbiş

Title:
Transcatheter Aortic Valve Replacement for Asymptomatic Severe Aortic Stenosis: Results of EARLY TAVR Trial

Presentation at: TCT 2024

Link:  https://www.nejm.org/doi/pdf/10.1056/NEJMoa2405880

Introduction

Aortic stenosis (AS) is a significant health issue, affecting over 3% of adults, particularly those over 65 years of age. Current ESC and ACC/AHA guidelines primarily recommend aortic valve replacement (AVR) for patients with symptomatic severe AS. In asymptomatic patients, however, valve replacement is indicated only under specific conditions, including left ventricular ejection fraction (LVEF) below 50%, very severe AS, high calcification scores, or if there are other indications for cardiac surgery. For these asymptomatic patients, clinical and echocardiographic follow-up every 6 to 12 months is the recommended approach.

While evidence supports early surgical AVR as beneficial for asymptomatic AS patients, data are lacking on the efficacy of transcatheter aortic valve replacement (TAVR) for asymptomatic AS without additional imaging or laboratory evidence of systolic or diastolic dysfunction. A randomized study is required to reassess current practices and evaluate the potential advantages of TAVR in this patient population.

Objective

This study aims to investigate the effect of early TAVR on clinical outcomes in patients with asymptomatic severe AS.

Methods

The EARLY TAVR trial is a prospective, multicenter, open-label, randomized, controlled study comparing balloon-expandable TAVR (SAPIEN 3 or SAPIEN 3 Ultra, Edwards Lifesciences) with guideline-directed clinical surveillance in asymptomatic patients with severe AS. Eligible patients were those aged 65 and older with severe AS and suitable for transfemoral TAVR. Exclusion criteria included a Society of Thoracic Surgeons (STS) Predicted Risk of Mortality score over 10%, LVEF below 50%, or another Class I indication for AVR. Asymptomatic status was confirmed via treadmill stress testing, or, if testing was not feasible (e.g., due to orthopedic limitations), determined by a comprehensive medical history review by a specialist.

Patients with asymptomatic severe AS were randomized in a 1:1 ratio to either clinical surveillance or TAVR with the Edwards SAPIEN 3/SAPIEN 3 Ultra transcatheter valve. The primary endpoint was a composite of all-cause mortality, stroke, or unplanned cardiovascular hospitalizations. In the clinical surveillance group, aortic valve interventions within the first six months post-randomization were counted as unplanned hospitalizations for cardiovascular causes. A minimum follow-up duration of two years was planned per trial design.

Results

Between March 2017 and December 2021, a total of 1,578 patients were screened across 75 centers in the United States and Canada, with 901 patients ultimately randomized: 455 to the TAVR group and 446 to the clinical surveillance group. The mean age of participants was 75.8 years, with an average STS Predicted Risk of Mortality score of 1.8%, and 83.6% of patients were classified as low surgical risk. Primary endpoint events occurred in 122 patients (26.8%) in the TAVR group and in 202 patients (45.3%) in the clinical surveillance group (HR, 0.50; 95% CI, 0.40–0.63; P<0.001).

Analysis of the primary endpoint components revealed similar all-cause mortality rates between the TAVR (8.4%) and clinical surveillance groups (9.2%) (HR 0.93; 95% CI, 0.60–1.44). The TAVR group showed a trend towards lower stroke incidence (4.2% vs. 6.7%; HR 0.62; 95% CI, 0.35–1.10). Unplanned cardiovascular hospitalizations were significantly lower in the TAVR group (20.9%) compared to the clinical surveillance group (41.7%). Of the 186 unplanned hospitalizations in the clinical surveillance group, 105 were due to aortic valve interventions within six months post-randomization. After a median follow-up of 3.8 years, 87% of patients in the clinical surveillance group had undergone aortic valve replacement. Adverse events associated with the procedure were comparable between TAVR recipients and those in the clinical surveillance group who later underwent AVR.

Conclusions

Early TAVR in asymptomatic severe AS patients demonstrated superiority over guideline-directed clinical surveillance in reducing composite endpoints, including death, stroke, and unplanned cardiovascular hospitalizations over a two-year follow-up period.

Commentary

The EARLY TAVR trial fills a critical gap in the literature on the management of asymptomatic severe AS. While current guidelines emphasize symptoms as a key factor for intervention in severe AS, recent discussions have focused on whether these asymptomatic patients are truly asymptomatic. Although asymptomatic status was confirmed in this trial, early TAVR was shown to be superior to clinical surveillance.
A crucial insight from the study is that the clinical surveillance group essentially served as a delayed TAVR group, with one in four patients undergoing AVR within six months, and one-third developing symptoms attributable to AS. These findings suggest that once severe stenosis is established echocardiographically, symptoms may manifest within a relatively short period, around 6 to 12 months.

Ideally, earlier intervention may prevent progressive left ventricular damage and the subsequent development of heart failure, atrial fibrillation, and left ventricular dysfunction. However, the similar mortality rates across both groups reinforce the suitability of current practices, as unplanned hospitalizations in the surveillance group were largely attributed to AVR for cardiovascular indications.

Although further debate is warranted on whether these findings will alter future guideline indications, this study represents a cornerstone in understanding the natural history of AS and informs management for a substantial patient population in clinical practice.