Design and rationale of the evaluation of transcatheter aortic valve replacement compared to surveillance for patients with asymptomatic severe aortic stenosis: The EARLY TAVR trial.

BACKGROUND: For patients with asymptomatic, severe aortic stenosis (AS) and preserved left ventricular ejection fraction, current guidelines recommend clinical surveillance every 6 to 12 months. To date, no randomized trials have examined whether an early intervention with transcatheter aortic valve replacement (TAVR) will improve outcomes among these patients. STUDY DESIGN AND OBJECTIVES: EARLY TAVR is a prospective, randomized, controlled, and multicenter trial, with an event-based design. Asymptomatic severe AS patients (n = 900) are randomized 1:1 to either clinical surveillance or TAVR with the Edwards SAPIEN 3/SAPIEN 3 Ultra transcatheter heart valve. Patients are stratified by whether they are able to perform a treadmill stress test. The primary end point is death, stroke, or unplanned cardiovascular hospitalization. Patients who are asymptomatic but have a positive stress test will be followed in a registry and undergo aortic valve replacement as per current guidelines. CONCLUSIONS: EARLY TAVR is the largest randomized trial to date assessing the role of early intervention among patients with asymptomatic severe AS compared to clinical surveillance and the first to study the role of TAVR. TRIAL REGISTRATION NUMBER: NCT03042104.

Bicuspid Aortic Valve Morphology and Outcomes After Transcatheter Aortic Valve Replacement.

BACKGROUND: Bicuspid aortic stenosis accounts for almost 50% of patients undergoing surgical aortic valve replacement in the younger patients. Expanding the indication of transcatheter aortic valve replacement (TAVR) toward lower-risk and younger populations will lead to increased use of TAVR for patients with bicuspid aortic valve (BAV) stenosis despite the exclusion of bicuspid anatomy in all pivotal clinical trials. OBJECTIVES: This study sought to evaluate the association of BAV morphology and outcomes of TAVR with the new-generation devices. METHODS: Patients with BAV confirmed by central core laboratory computed tomography (CT) analysis were included from the international multicenter BAV TAVR registry. BAV morphology including the number of raphe, calcification grade in raphe, and leaflet calcium volume were assessed with CT analysis in a masked fashion. Primary outcomes were all-cause mortality at 1 and 2 years, and secondary outcomes included 30-day major endpoints and procedural complications. RESULTS: A total of 1,034 CT-confirmed BAV patients with a mean age of 74.7 years and Society of Thoracic Surgeons score of 3.7% underwent TAVR with contemporary devices (n = 740 with Sapien 3; n = 188 with Evolut R/Pro; n = 106 with others). All-cause 30-day, 1-year, and 2-year mortality was 2.0%, 6.7%, and 12.5%, respectively. Multivariable analysis identified calcified raphe and excess leaflet calcification (defined as more than median calcium volume) as independent predictors of 2-year all-cause mortality. Both calcified raphe plus excess leaflet calcification were found in 269 patients (26.0%), and they had significantly higher 2-year all-cause mortality than those with 1 or none of these morphological features (25.7% vs. 9.5% vs. 5.9%; log-rank p < 0.001). Patients with both morphological features had higher rates of aortic root injury (p < 0.001), moderate-to-severe paravalvular regurgitation (p = 0.002), and 30-day mortality (p = 0.016). CONCLUSIONS: Outcomes of TAVR in bicuspid aortic stenosis depend on valve morphology. Calcified raphe and excess leaflet calcification were associated with increased risk of procedural complications and midterm mortality. (Bicuspid Aortic Valve Stenosis Transcatheter Aortic Valve Replacement Registry; NCT03836521).