SAN DIEGO, CA—Clinical surveillance appears to be an inferior approach for managing patients with moderate aortic valve stenosis accompanied by high-risk features, according to results of the PROGRESS trial.
Over 2 years, the risk of death or a heart failure (HF) event with or without hospitalization was significantly lower among patients treated with transcatheter aortic valve implantation (TAVI) compared with clinical surveillance in patients with moderate aortic stenosis and at-risk features, such as valve-related symptoms and/or structural or functional abnormalities, reported investigators today at TCT 2026.
“Moderate aortic stenosis is not benign,” said lead researcher Philippe Généreux, MD (Morristown Medical Center, New Jersey), during a morning press conference. “These patients will benefit from further referral to a valve center for a comprehensive evaluation to establish the optimal management strategy. Rather than waiting for progression to severe aortic stenosis, PROGRESS supports TAVI for patients with moderate aortic stenosis and at-risk features.”
TAVI is currently approved for patients with severe aortic stenosis at low, intermediate, and high risk for surgery and asymptomatic patients with severe aortic stenosis. PROGRESS is the first randomized, controlled trial investigating the benefit of TAVI in patients with moderate aortic stenosis.
Rishi Puri, MD, PhD (Cleveland Clinic, OH), who wasn’t involved in the study, told Cardiology Now News that PROGRESS is one of the most important clinical trials in aortic stenosis since PARTNER was presented in 2010.
“In my opinion, it’s even more impactful than the low-risk trials because it fundamentally changes how we look at the valve,” he said. “What it teaches us is that we should not be looking at the valve in isolation and that we need to get out of the mentality of arbitrary cutoffs for human pathology. Mother nature exists on a continuum and every human is different. When you have an outflow obstruction, whether it’s moderate or severe, some people don’t fare very well.”
PROGRESS, he said, demonstrates that in people with evidence of subclinical or clinical HF, addressing the outflow obstruction “can make a fundamental difference to the natural history of these patients.”
During the late-breaking session, Stephan Windecker, MD (Bern University Hospital, Switzerland), made a similar point, saying the field should move away from a binary classification of aortic stenosis severity and shift toward a multidimensional assessment of patient risk across the moderate-to-severe aortic stenosis spectrum.
“I think we should move forward and call it ‘clinically significant’ aortic stenosis,” Généreux added. “Give back the power to the physician to use their clinical judgement to [determine] if the procedure will help the patient.”
Better Outcomes at 2 Years
The study, published simultaneously in the New England Journal of Medicine, included 744 patients (mean age 78.4 years; 39.1% women) with moderate aortic stenosis randomized at 74 sites across 6 countries. Patients were eligible if they had moderate aortic stenosis based on echocardiographic criteria and at least one high-risk feature, such as valve-related symptoms, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP), reduced left ventricular ejection fraction (LVEF), grade 2 or higher diastolic dysfunction, atrial fibrillation, elevated aortic valve calcium score assessed by computed tomography, or a reduced stroke-volume index.
Most patients (91%) had concordant aortic stenosis where both the valve area and velocity or gradient measurements were in the moderate range.
A total of 1,294 patients were screened, with the absence of moderate aortic stenosis on echocardiography the most common reason for screen failure. Among those randomized, more than 96% were symptomatic (NYHA ≥ II) and 44% had evidence of diastolic dysfunction. Overall, 72% of patients had two or more at-risk features.
At 2 years, the primary endpoint of death or HF event with or without hospitalization occurred in 23.9% of those treated with clinical surveillance and 16.7% of those who underwent TAVI (HR 0.67; 95% 0.48-0.93). There was no difference in mortality, but HF events were significantly lower in those treated with TAVI: 10.8% vs 19.0% with clinical surveillance (HR 0.55; 95% 0.37-0.81). HF hospitalizations occurred in 7.4% of TAVI-treated patients compared with 14.9% of those under clinical surveillance (HR 0.48; 95% 0.30-0.77).
The procedure was also safe: the 30-day incidence of death from any cause, stroke, life-threatening or fatal bleeding, stage 4 kidney injury, hospitalization for device- or procedure-related complication, or valve dysfunction was 5.9%, which fell within the prespecified performance goal of 13.7%. There were no deaths and a low incidence of stroke (0.8%) in the TAVI-treated patients. A quality-of-life analysis showed there was an “immediate and clinically significant improvement” in the Kansas City Cardiomyopathy Questionnaire in those treated with TAVI.
Généreux stressed that PROGRESS investigators used a rigorous definition of HF events. To be counted, three criteria needed to be met: 1) present with new or worsening HF symptoms; 2) present with least two objective criteria, such as peripheral edema or increased NT-proBNP; and 3) escalation of HF treatment.
In those randomized to surveillance, 27.0% progressed to aortic valve replacement by 1 year and 57.4% by 2 years. Among these 204 patients in the watchful-waiting arm who required aortic valve replacement, more than 80% had progressed to severe aortic stenosis.
Généreux told Cardiology Now News that a substantial number of patients were not suitable for TAVI, with 550 screened out. For those with anatomy unsuitable for TAVI, surgery may be an option, but it is not known if surgery can match the safety profile of TAVI in this setting. “When you go earlier in the disease stage, you need to make sure the procedure or the device is safe compared to the risk-benefit ratio,” he said.
Getting a Handle on Patient Size
Patrick O’Gara, MD (Brigham and Women’s Hospital, Boston, MA), a member of the TCT panel, said there is an “entire universe” of patients with moderate aortic stenosis and a high burden of comorbidities like those enrolled in PROGRESS.
“I do think clinicians will have difficulty in terms of teasing out symptoms that are referrable to the aortic stenosis versus those that might be referrable to atrial fibrillation, coronary artery disease, and diastolic dysfunction that could exist for independent reasons,” said O’Gara. Nonetheless the trial showed that among this select group of older, highly symptomatic patients, eliminating the left ventricular afterload could improve short-term quality of life and reduce the incidence of heart failure events, he said.
There are limitations to PROGRESS, including the relatively short follow-up and open-label design. During the discussion, Généreux said that TAVI in appropriate patients with moderate aortic stenosis can be advantageous because the valve can be fully expanded, which could translate into better long-term performance. However, 10-year follow-up is necessary to better understand the durability question.
Puri isn’t concerned about durability too much, noting that patients in PROGRESS were older than those included in the low-risk TAVI trials. Like Généreux, he believes the moderate aortic stenosis setting may be more amenable to the minimally invasive procedure.
“These valves may be a little less calcified,” said Puri, “and so our ability to expand our stent frames may be easier. We know that stent-frame expansion dials into valve durability. We’re still only understanding this and appreciating it now. Would durability in a moderate aortic-stenosis substrate be better, or slightly better than in severe aortic stenosis? Maybe. Our stent frames are more symmetrical, but I think it really goes to the point that if you have calcified ‘rocks’ in your leaflets, you’ve really missed the boat in many ways.”
Source:
Généreux P, Makkar RR, Pibarot P, et al. TAVR in patients with moderate aortic stenosis with at-risk features. N Engl J Med. Published online November 2, 2026.
Disclosures:
Généreux reports consulting fees/honoraria from Abbott Vascular, Cardiawave, Edwards Lifesciences, Egnite, EchoIQ, Haemonetics Corporation, Medtronic, 4C Medical, Puzzle Medical inc, Pi-Cardia, Antegrade Medical, and Spiralis medical inc.; Equity in Cardiawave, EchoIQ, Sparrow Bioacoustics, Pi-Cardia, Puzzle Medical inc, Antegrade Medical, and Spiralis.
Windecker reports grant/research support from Abiomed; Amgen; AstraZeneca; Bayer AG; B. braun; Biotronik; Boehringer Ingelheim; Boston Scientific Corporation; Bristol-Myers Squibb; Edwards Lifesciences; Fumedica; Guerbet; Janssen Pharmaceuticals; MedAlliance; Medtronic; Novartis; Pfizer; Sanofi-Aventis; Servier; Sinomed; Cordis Corporation; Corflow Therapeutics; CSL Behring; Daiichi-Sankyo/Elil Lilly and Company; Johnson &J ohnson; V-Wave; Abbott; GE Healthcare; Inari Medical; Novo Nordisk; Philips; Siemens Healthcare; SMT; MSD Merck Sharp&Dohme; Amicus Therapeutics; Bioanalytica; IACULIS; OM Pharma; Orchestra BioMed; Vascular Medical; Alnylam; Anteris; Anandic Medical Systems; Linde Gas; TRiCares GmbH; and Zoll.
Puri and O’Gara report no conflicts of interest.