Research possible harbinger for broader intervention guidelines treating AS

Two research studies by Egnite Inc. presented at the American College of Cardiology Conference (ACC) were recently featured in BioWorld™ MedTech.

David Godkin – Thursday, March 16th, 2023

Two research studies by Egnite Inc. presented at the American College of Cardiology Conference (ACC) could shake up the scope of how aortic stenosis (AS) is understood and treated by physicians. Research team leader Philippe Généreux said key findings demonstrated increased mortality across all degrees of severity of AS, suggesting the need to re-evaluate current guidelines for clinical intervention.

“This is really exciting because it’s one of the largest ever data bases presented on AS using natural language processing, capturing and working from more than 1.6 million real world echocardiograms,” Généreux told BioWorld. “Now we can start to tap into this large data base to try to gather more information about patients and this specific disease.”

Timing is everything

In addition to the magnitude of the data presented at the conference is the fact in the real world cardiologists are presented with patients with less severe AS that must still be treated effectively. What they need to know, said Généreux, is optimal timing in which to intervene to improve their patient’s prognosis.

To date ACC guidelines recommend intervening when AS is deemed severe, i.e., when the aortic valve area (AVA) is less than 1 cm square, and an echocardiogram shows a mean pressure gradient above 40. New data from the Egnite studies suggest doctors may be waiting too long to implant a new aortic valve and might do so before the AVA measures less than 1 cm square.

“There’s no dogma in nature that at 1.1 square centimeters you’re okay and at that at less than 1.1 square centimeters you’re not,” said Généreux. “A lot of data shows perhaps even mild to moderate stenosis could be associated with detrimental prognoses, so perhaps we could be a little more aggressive when treating those patients.”

This means more immediate action to prevent cardiac damage and decreased heart function by changing the heart valve through surgery or transcatheter aortic valve replacement, said Généreux. It might also impact patient follow-up after a patient is diagnosed with mild AS, as it evolves towards more moderate and even severe AS.

“And sometimes does so pretty quickly,” Généreux added. He drew a parallel with cancer, i.e., not waiting for a cancer detected at an early stage to evolve to a more advanced stage of the disease before treating it. “If you have a benign tumor with the potential to become a cancer you don’t sit on it for five years,” Généreux said. “Instead, you might follow this patient more frequently, perhaps every year with biomarker blood testing and CT scans to further assess the severity of the disease.”

In addition to better understanding the different levels of severity in AS, earlier intervention might mitigate risk in helping cardiologists correctly pinpoint the severity of AS their individual patients are experiencing. “This third finding is very important,” said Généreux. “It points to a continuum of severity evolving differently in patients based on their specific vulnerability.”

Cardiac damage, mortality

The first study used Aliso Viejo, Calif.-based Egnite’s extensive database to validate AS staging based on cardiac damage in untreated patients across all levels of AS severity. Among patients with the disease the study found high prevalence of cardiac damage that included left ventricular hypertrophy, systolic and diastolic dysfunction, atrial fibrillation and pulmonary hypertension.

“If you’re not sure of the severity of AS in a patient then absolutely you need to integrate other variables such as the extent of cardiac damage,” said Généreux. “This means having a big picture of where the AS may be moderate, but heart function has already dropped, or there’s already enlargement of the left atrium or Afib that leaves the patient very vulnerable.”

The second study assessed untreated mortality across all documented degrees of severity of AS, and drew particular attention to use of Egnite’s real-world database at 24 leading teaching and non-teaching institutions across the U.S. There, natural language processing software was used to scan the charts of patients, looking for AS severity across more than 1.6 million patients with some degree of the disease.

Among this study’s key findings was that incrementally increased mortality across all degrees of severity for AS suggest the need to re-evaluate currently recommended timing of intervention.

Cardiologists told Généreux they were “shocked” to learn mild to moderate stages of AS could be far worse for patients than originally believed and agreed they needed to do a better job tracking and potentially treating these patients earlier.

But it’s one thing to be impressed by a massive database and draw conclusions around early diagnosis and treatment of a disease; it’s quite another to lead the charge changing current treatment guidelines. The next step, said Généreux, is introducing strong evidence from randomized clinical trials to the ACC and American Heart Association (AHA).

His team is in the process of doing just that through three randomized clinical trials using aortic valve replacement for moderate AS.

“If after two or three years of intervention with TAVR and open surgery to replace the valve there are benefits to patients, the ACC/AHA will ask if the evidence is sufficient to elevate the recommendation to moderate AS,” said Généreux. “This is where clinical practice could begin to change, he added.

Généreux was asked if advances in medical technologies have any role in supporting clinical practice changes that result from new intervention AS guidelines. “If we intervene earlier obviously, we will need aortic valves that last a long time particularly if patients live 25 or 30 years,” he replied.

“Tissue reengineering or techniques to modify or correct an existing bodily valve might be developed so that valve implants may not even be required. There’s a lot of enthusiasm in light of this new data,” said Généreux.

©2023 BioWorld. Reprinted with permission from Clarivate.

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