Majority of Patients with Moderate Aortic Stenosis Carry Features Linked to Twice the Risk of Death, egnite Registry Study Finds

The analysis, published simultaneously in JACC, found that moderate AS patients with at least one at-risk feature had a two-fold increase in mortality and hospitalization with heart failure compared with moderate AS patients with no at-risk features over two years.

Dr. Philippe Généreux also announced ACTIVATE AS, the first prospective multicenter study to use the CardioCare® platform to identify and follow patients with moderate AS.

SAN DIEGO, Nov. 2, 2026 /PRNewswire/ — In a real-world study of more than 53,000 patients with aortic stenosis (AS) at 48 U.S. institutions, moderate AS outnumbered severe AS nearly 2 to 1, and 78.7% of patients with moderate AS had at least one at-risk feature. Over two years, those patients had twice the rate of mortality and hospitalization with heart failure as moderate AS patients without at-risk features, according to data presented today by Philippe Généreux, MD, Director, Structural Heart Program at Atlantic Health Morristown Medical Center, at TCT 2026 San Diego and published simultaneously in the Journal of the American College of Cardiology (JACC).

The study analyzed de-identified data from the egnite Registry, covering nearly 15 million patients and 6.5 million echocardiograms with appropriate permissions, making it the largest study of moderate AS outcomes to date.

Dr. Généreux also announced ACTIVATE AS, a prospective, multicenter study that will use the CardioCare platform to identify approximately 700 patients with moderate AS and follow them rigorously in a dedicated valve clinic with multiparametric evaluation every six months. It is the first prospective clinical study to use CardioCare, with enrollment expected to begin in 2027.

Key findings

Among 53,994 patients with moderate or severe AS identified since January 2022:

• Moderate AS outnumbered severe AS nearly 2 to 1 in this cohort (35,343 vs. 18,651 patients). Of the moderate patients, 78.7% had at least one at-risk feature: valve-related symptoms, left ventricular ejection fraction below 60%, grade 2 or higher diastolic dysfunction, low stroke volume index, atrial fibrillation, or elevated natriuretic peptides. Excluding symptoms, 69.9% still had at least one at-risk feature.
• At-risk features were associated with double the risk of death and hospitalization with heart failure. Two-year mortality was 20.1% for moderate AS patients with at-risk features vs. 9.0% without. Hospitalization with heart failure was 44.6% vs. 21.9%. After multivariable adjustment, including for comorbidities, at-risk features remained associated with roughly twice the risk of death and hospitalization with heart failure.
• Most events occurred while patients were still labeled as moderate. On the last echocardiogram before the event, 86% of hospitalizations with heart failure and 90% of deaths among moderate AS patients occurred while still moderate, without evidence of progression to severe AS.

Current ACC/AHA guidelines recommend echocardiographic surveillance every one to two years for moderate AS, with valve replacement deferred until severe criteria are met. In the study, 20% to 23% of moderate AS patients underwent valve replacement documented by the contributing health system within two years, compared with 50.1% of patients with severe AS.

ACTIVATE AS prospective study

ACTIVATE AS (Activating Patients with Moderate AS) is a prospective, multicenter, observational study of patients with moderate AS. Atlantic Health Morristown Medical Center will serve as the lead site and coordinating center, and enrollment is expected to begin in 2027.

The study will use the CardioCare platform to identify approximately 700 patients with moderate AS across participating sites, grouped by disease phenotype. Patients will be recalled for heart team evaluation, including echocardiography assessed by a core laboratory, natriuretic peptide testing and CT aortic valve calcium scoring. Patients in the study will be followed every six months for up to two years or until they develop severe AS or undergo an aortic valve replacement. ACTIVATE AS is an investigator-initiated study led by Dr. Généreux and funded by an unrestricted grant from Edwards Lifesciences.

“This is CardioCare’s first use in a prospective, multicenter study to identify and follow patients, building on the egnite Registry,” said Rahul Sharma, MBBS, FRACP, Director of Structural Interventions and Associate Director of the Cardiac Catheterization Laboratory at Stanford Health Care, Senior Medical Advisor of egnite, and co-author of the Moderate Aortic Stenosis with At-risk Features study. “The Registry identifies where risk concentrates in moderate AS; ACTIVATE AS will evaluate these patients in clinical practice through structured assessments and six-month follow-up. Over time, this evidence could help guide monitoring intervals for patients with moderate AS.”

About the study

The analysis used de-identified EHR and echocardiographic data from the egnite Registry, covering 14,859,523 patients and 6,514,171 echocardiograms at 48 U.S. institutions with appropriate permissions. It included adults diagnosed with native-valve moderate or severe AS on or after Jan. 1, 2022, and received exemption from Institutional Review Board review. The full manuscript, “Moderate Aortic Stenosis with At-risk Features,” is available in JACC.

AS severity was graded from quantitative valve measurements in echocardiography reports according to American Society of Echocardiography guidelines. The analysis was supported by a study grant from Edwards Lifesciences. Findings are observational; full methods and limitations are available in the JACC publication.

About egnite, Inc.

egnite, Inc. is a technology company advancing guideline-directed cardiovascular care and real-world evidence. egnite’s CardioCare® platform is deployed at more than 80 heart programs, drawing on data from more than 1,200 cardiovascular care facilities, to identify and prioritize cardiovascular patients. CardioCare combines practical AI, clinical logic aligned to ACC/AHA guidelines and workflow integration to help hospitals move more patients into evidence-based care pathways. The egnite Registry, built on de-identified EHR data with appropriate permissions from 15.7 million patients and 6 million echo reports, gives life sciences and research teams a longitudinal view of the patient journey. The company is headquartered in Aliso Viejo, California. For more information, visit www.egnitehealth.com.

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SOURCE egnite Health

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