Early transcatheter aortic valve replacement prevented declines in left ventricular and atrial health among patients with asymptomatic severe aortic stenosis, according to a sub-analysis of the EARLY TAVR trial presented at the American Society of Echocardiography (ASE) 2025 Scientific Sessions and published in the Journal of the American Society of Echocardiography and JACC.

Whether patients had normal or abnormal measures of left ventricular health at baseline, all patients with severe aortic stenosis (AS) experienced a benefit from early intervention with transcatheter aortic valve replacement (TAVR) in comparison with clinical surveillance alone. 

“I strongly believe that based on these findings...early referral and prompt aortic valve replacement should be the preferred strategy for all patients with severe aortic stenosis, regardless of symptom status,” said study investigator Philippe Généreux, MD, an interventional cardiologist at the Gagnon Cardiovascular Institute, Morristown Medical Center, Morristown, New Jersey, when presenting the findings of the analysis during the ASE 2025 meeting.

Background

For patients with asymptomatic severe AS and preserved left ventricular ejection fraction, guidelines recommend routine clinical surveillance. On the other hand, patients with severe AS and abnormal left ventricular structure or function are recommended by ACC/AHA guidelines to receive early intervention as they are more likely than patients with normal left ventricular health to benefit from this early intervention. 

The EARLY TAVR trial was a randomized, controlled trial that looked at the use of TAVR in comparison with traditional clinical surveillance in this patient population. A total of 901 patients across 75 centers were randomly assigned 1:1 to undergo either early TAVR with transfemoral placement of a balloon-expandable valve or clinical surveillance.

Primary endpoint results from the study showed that early TAVR was superior to clinical surveillance for reducing the composite risk of all-cause death, stroke, or unplanned hospitalization due to cardiovascular issues in patients with severe AS at a minimum of 2 years of follow-up. In the TAVR arm, the composite risk was 26.8% compared with 45.3% in the clinical surveillance arm (P < .001). 

Study Methods

Integrated left ventricular/left atrial health was a pre-specified secondary endpoint of the EARLY TAVR study.

For the analysis, the researchers looked at echocardiographic data collected from patients at baseline, pre-procedure for patients in the control arm who converted to aortic valve replacement, 30 days after, and 1, 2, 3, and 5 years after randomization and post procedure. For the sake of the study, integrated left ventricular/left atrial health was defined as the composite of absolute left ventricular global longitudinal strain of at least 15%, left ventricular mass index of under 115 g/m² for men or under 95 g/m² for women, and left atrial volume index of up to 34 mL/m².

Patient Characteristics

In the TAVR arm, patients had a mean age of 76 and in the surveillance arm the mean was 75.6 years. Less than one-third (28.8%) of patients in the TAVR arm and a third of patients in the surveillance arm were women. In both arms, the baseline mean left ventricular ejection fraction was 67.4%.

In the clinical surveillance arm, 87% converted to aortic valve replacement with a median time to conversion of 11.1 months.

About 93% of patients had evaluable echocardiographic data to analyze integrated left ventricular/left atrial health.

At baseline, 27% of patients had normal integrated left ventricular health and 73% had abnormal measures of left ventricular health, which comprised of three criteria: left ventricular diastolic function, left ventricular structure, and left ventricular systolic function. 

Secondary Endpoints

Secondary endpoints from the Early TAVR trial showed that overall integrated left ventricular health at 2 years of follow-up was greater in the TAVR arm compared with the surveillance arm at 48.1% vs 35.9%, respectively (P = .001). This integrated value comprised of individual criteria of a normal left ventricular mass index of 82.6% in the early TAVR arm and 72.1% in the surveillance arm (P < .001); normal left atrial volume index of 55% vs 45.6%, respectively (P = .012); and a normal left ventricular global longitudinal strain of 96.1% vs 92.8% (P = .052). 

Favorable health status outcome—a measure of patient quality of life—was significantly improved with early intervention with TAVR; the outcomes rates were 86.6% in the early TAVR arm vs 68% in the surveillance arm (P < .001). 

Additional Findings

When looking at overall integrated left ventricular health, patients with abnormal health measures were more likely to experience death, stroke, or heart failure hospitalization at a rate of 26.5% at 60 months vs 15.9% for patients with normal integrated left ventricular health (P = .02). 

For the individual criteria, patients with enlarged left ventricular diastolic function had a rate of death, stroke, or heart failure hospitalization at 60 months of 27.2% vs 19.4% for patients with normal left ventricular diastolic function (P = .02); left ventricular hypertrophy led to a rate of 33.1% at 60 months vs 19.0% for patients with normal left ventricular structure (P < .0001); and patients with impaired left ventricular systolic function had a rate of 34.5% vs 22.1% for normal function at 60 months (P = .008). 

For integrated left ventricular health overall, the risk for death, stroke, or unplanned cardiovascular hospitalization was increased if the patient had abnormal health measures vs normal health. For the mitigation of all risks, early TAVR was better than clinical surveillance. 

Patients with abnormal integrated left ventricular health were more likely to have acute valve syndrome than those with normal integrated health measures, including symptoms of syncope, atrial fibrillation, ventricular arrhythmia, left ventricular ejection fraction drops under 50%, and more. 

Patients with normal and abnormal integrated left ventricular health in the clinical surveillance arm had similar rates of conversion to aortic valve replacement (AVR); at 60 months, the rates were 95.7% and 94.7%, respectively (P = .60). "We saw, actually, that conversion to AVR in the patients randomized to the waiting group was very similar whether they have normal or abnormal LV. At 2 years, almost 70% of patients required an AVR," Dr. Généreux said.

Conclusions and Clinical Implications

Dr. Généreux noted that abnormal left ventricular health was associated with increased event rates, but the early TAVR strategy provided consistent benefit for patients regardless of baseline integrated left ventricular health status. 

Patients in the surveillance arm showed worse left ventricular health at 2 years than those who were treated early, supporting recommendations for early intervention. 

He noted, though, that baseline measures of integrated left ventricular health did not serve as a predictive biomarker for the timing of conversion to delayed aortic valve replacement. "These findings suggest the limited value of measured left ventricular health to guide timing of intervention," Dr. Généreux said.

When asked during the presentation what other biomarkers should be explored to be able to triage patients more likely to experience an event, he stressed focusing on patients with normal left ventricular health before their AS becomes severe and their health measures decline, and he suggested that these patients see a specialist and begin preparing for an eventual or possible aortic valve replacement.