On Monday, February 28, 2022, Dr. Ron Waksman presented the late-breaking four-year follow-up to the Low Risk TAVR (LRT) trial, which was an investigator-initiated, multicenter, prospective study of low-risk patients with symptomatic, severe aortic stenosis, undergoing TAVR with a balloon-expandable or self-expanding transcatheter heart valves (THV). Of note, this was also the first U.S. Food & Drug Administration-approved investigational device exemption (IDE) trial investigating the feasibility of TAVR in a low-risk cohort of patients. The enrollment period spanned January 2016- February 2018, predating the FDA’s expanded indication approval for low-risk TAVR in August 2019. The topline findings of this trial supported the conclusion that TAVR remains safe and effective at 4 years following THV implantation.   

In total, 200 low-risk patients with symptomatic, severe aortic stenosis, undergoing transfemoral implantation of a commercially available TAVR valve, were enrolled at 11 low-moderate volume centers and were followed for the primary endpoint of 30-day all-cause mortality (VARC II-defined). Patients were included if they had tricuspid aortic stenosis and were low risk as defined by STS PROM < 3% and had a life expectancy > 1 year.  Exclusion criteria mainly comprised severe noncardiac disease or organ failure or need for alternative access. The purpose of this analysis was to report the clinical outcomes and hemodynamic status of the THVs at 4 years. The mean age was 73.6 years, and 61.5% were male with preserved LVEF (63.5 + 7.5%).  Balloon-expandable THVs were used in 88.2% of patients and self-expanding valve in 11.8%. The rate of all-cause mortality was 0% at 30-days, 3% at 1 year, 4.1% at 2 years, 8.2% at 3 years and 12.1% at 4 years (21/174 patients available for follow-up). Incidence of all strokes was 7.9% (disabling stroke 2.0%).  At 30-day follow-up hypo-attenuated leaflet thickening (HALT) was seen in 14% of TAVR recipients. At four years, HALT ostensibly did not impact clinically relevant THV hemodynamics as assessed by LVEF (HALT: 65.5% ± 4.2% vs. no HALT: 64.9% ± 5.8%; p=0.84), LV end-diastolic dimension (HALT: 4.1 ± 0.4 cm vs. no HALT: 4.3 ± 0.6 cm; p=0.48), mean aortic valve gradient, aortic valve area and dimensionless index.  It should be noted that the HALT data represents a smaller subset (76/200) of the overall number of patients enrolled in LRT and thus the structural valve deterioration finding should be interpreted in that context. 

Why is this study important?

Transcatheter aortic valve replacement (TAVR) is a well-established treatment for severe aortic stenosis and is now the preferred therapy for patients over the age of 80 or life expectancy of less than 10 years.  TAVR is now being offered to younger and lower risk patients after multiple clinical trials demonstrated the safety and efficacy of TAVR in low-risk patients.  However, valve durability continues to come into question when deciding between TAVR and SAVR in our younger, lower risk patients. The four-year data of the Low-Risk Trial (LRT) is important because it expands our understanding of valve durability and continues to support the use of TAVR in low risk patients.

Should I change my practice because of these findings?

The results of the LRT trial should not change your practice, but rather support our current practice.  In patients with aortic valve disease who are low surgical risk, shared decision making between the patient and the heart valve team is essential in determining whether a patient undergoes TAVR or SAVR. 

What question was this study supposed to answer?

This study was the first FDA approved investigational device exemption study to evaluate the safety and feasibility of TAVR in low-risk patients with either balloon expandable or self-expanding commercially available valves. The objectives of the LRT four-year trial results were 1) assess clinical outcomes and hemodynamics outcomes at 4 years 2) report the impact of hypo-attenuated leaflet thickening (HALT). 

What did the study show?

The LRT trial four-year results maintained low clinical event rates including mortality and stroke as well as excellent valve hemodynamics.  While the number of HALT patients were low in this study, HALT did not adversely affect valve hemodynamics or increase the structural valve deterioration at 4 years. The LRT trial continues to support the use of TAVR in a low-risk population. 

How good was the approach/methodology?

An important aspect of the LRT trial is that it represents a more real-world experience as the enrolled sites were not high volume centers and had not been enrolled in the pivotal clinical trials.  However, all cases were appropriately adjudicated with similar methods compared to the pivotal trials. The importance of the LRT trial is that while it was an observational trial it mirrored the results of two other landmark low risk TAVR trial.   

All authors: Tamara Atkinson, MD, FSCAI and Sandeep Nathan, MD, MSc, FSCAI