- While TAVI has become a transformative, less invasive option for treating aortic stenosis, long-term data raise concerns about its durability, particularly in younger, low-risk patients under 65 years of age.
- Recent five- to six-year outcomes from key randomized trials show higher stroke risk, increased pacemaker need, and a mid-term survival advantage for SAVR, underscoring the limitations of expanding TAVI to younger populations without long-term evidence.
- Calls to lower the age threshold for TAVI are premature and unsupported by current data, and clinical decisions should prioritize long-term outcomes and individualized Heart Team assessments rather than short-term convenience.
Transcatheter aortic valve implantation (TAVI) has dramatically changed the landscape of care for patients with severe aortic stenosis (AS), evolving from a palliative option for those deemed inoperable to a widely accepted alternative to surgical aortic valve replacement (SAVR) in high-risk groups. Its application has progressively expanded to include low- and intermediate-risk patients, mainly due to influential randomized controlled trials (RCTs). While early and mid-term outcomes have been encouraging, there is ongoing concern about potential long-term risks, particularly as the procedure is increasingly used in younger patients with longer life expectancy.
As extended follow-up results from RCTs continue to emerge, assessing the long-term effectiveness and safety of TAVI compared to SAVR in lower-risk populations remains a critical area of ongoing research. There is a growing enthusiasm that has led some to advocate lowering the age threshold for TAVI to below 65 years. This shift, though seemingly patient-friendly due to the less invasive nature of TAVI compared to SAVR, is not supported by current data and may carry long-term risks. Recent mid-term reports, RCTs, and real-world data highlight the need for caution, especially when considering treatment in younger, low-risk individuals.
Randomized Clinical Trial Limitations and Mid-term Results
Key RCTs with at least 5-year follow-up reports, such as PARTNER 2, PARTNER 3, Evolut Low Risk, UK TAVI, SURTAVI, and NOTION, have provided valuable insight into TAVI outcomes in low-to-intermediate-risk patients. However, these studies were not designed to assess outcomes in patients under the age of 65. Most participants had a mean age closer to 75, and subgroup analyses by age were not powered. Notably, PARTNER 3 5-year follow-up revealed a numerical survival advantage for SAVR after year three, with Kaplan–Meier curves crossing around 36 months. Although this difference was not statistically significant, it raises concerns about the long-term performance of TAVI.
At 6 years, according to the unpublished post-approval studies reports from the U.S. Food and Drug Administration (FDA), there is a clear difference in mortality favoring SAVR in the PARTNER 3 population (All-cause mortality: 14.6% [TAVI]; 11.9% [SAVR]), clearly depicting the divergent course of survival curves of the PARTNER 3 TAVI and SAVR populations during the mid-term follow-up. The recent 5-year reports from the UK TAVI trial presented at EuroPCR 2025 in Paris showed a significantly higher risk of stroke among patients from the TAVI group (Hazard ratio, 1.78 (95%CI, 1.16-2.73); P=0.01). Furthermore, the UK TAVI cohort showed significantly higher rates of conduction disturbance requiring permanent pacing in TAVI patients (9.2% vs. 17.7%; p < 0.001), with no differences in quality of life after 2 years and up to the reported 5 years.
The recently published 5-year results from the Evolut Low Risk trial (Forrest JK et al., JACC 2025) reveal a near convergence of the curves for all-cause mortality or disabling stroke at five years. Additionally, the curves for non-cardiovascular mortality have already crossed, with SAVR demonstrating a lower, though not yet statistically significant, mortality rate at five years (6.2% vs. 6.8%). Furthermore, durability remains a significant unknown. Current TAVI devices lack long-term data beyond five years in younger low-risk patients. Even with favorable early outcomes, the potential for valve degeneration, paravalvular leaks, and pacemaker dependency increases with time. This is especially critical in patients with an average life expectancy of more than 5 years post-intervention. The current mean life expectancy of a 65-year-old person in Europe is 17 years for men and 21 years for women. With such a long remaining lifespan, decisions must prioritize sustainable solutions.
Redo Procedures and Post-TAVI Complications
TAVI in younger patients inherently increases the risk of future reintervention. Redo-TAVI and surgical TAVI explantation are on the rise, with surgical TAVI explantation being the fastest-growing operation in the US, and registry data indicating perioperative mortality rates of 15–18% after TAVI explant (Tang GHL, et al. JACC Cardiovasc Interv. 2023), which is nearly double what standard risk models predict. These reoperations are technically challenging and often unpredictable due to anatomical distortion caused by the initial TAVI.
In contrast, SAVR allows for a more controlled long-term treatment strategy. For example, a 60-year-old undergoing SAVR today might be a suitable candidate for a future valve-in-valve TAVI. The reverse (initial TAVI followed by SAVR) is more dangerous and less well-studied. A TAVI-first approach in young patients could create a generation of patients destined for high-risk redo procedures later in life.
Surgical Outcomes in Younger Patients Are Excellent
Modern SAVR techniques deliver outstanding results in younger, low-risk patients. STS registry data from over 42,000 SAVR procedures report 8-year survival rates of 92.9%, climbing to 95% in patients under 75 (Thourani VH, Ann Thorac Surg 2024). Furthermore, surgery offers other durable alternatives, such as SAVR with a mechanical valve or the Ross procedure. Contemporary series reporting results from experienced centers performing the Ross procedure show excellent long-term survival and freedom from reoperation. State-of-the-art mechanical valves have repeatedly demonstrated safety with low INRs (<2) without increasing the risk of thrombosis and significantly reducing the risk of bleeding.
Another important aspect among younger populations is the bicuspid aortic valve. A significant proportion of younger AS patients present with bicuspid aortic valves. The NOTION-2 trial recently demonstrated suboptimal outcomes for TAVI in this subgroup, underscoring the importance of cautious patient selection.
Methodological Red Flags and Industry Influence
Methodological concerns raise doubts about the generalizability and internal validity of low-risk TAVI RCTs, which were predominantly industry-sponsored. For example, the PARTNER 3 trial reported >10% loss to follow-up in the surgical arm, with considerably higher loss to follow-up in the surgical arm than in the TAVI arm. Similarly, in the Evolut Low Risk trial, a substantial proportion of patients in the surgical group received valve types that have since been withdrawn from the market due to known safety and durability concerns, such as the Trifecta and Mitroflow valves.
Furthermore, there have been several requests to the sponsors of these trials to make the data publicly available; however, to date, the data have not been made available for open independent analysis. The only independent investigator-initiated RCT studying low-risk patients is DEDICATE. This trial showed favorable results for TAVI up to 1 year. Nonetheless, results beyond the 1-year mark have not yet been reported. Interestingly, the outcomes from the surgical arm of DEDICATE were considerably poor, with unprecedentedly high mortality and stroke rates, never reported before in the literature.
This raises the question whether TAVI was actually good in the trial or maybe SAVR was extremely bad, instead highlighting the need for improving surgical standards in the centers that participated in the trial. Interestingly, a recent meta-analysis (Reddy et al., JACC 2025), which claimed to report updated long-term results from TAVI versus SAVR trials, concluded that in lower-risk patients, TAVI was associated with a reduced hazard of death and death or disabling stroke compared with SAVR.
However, the findings of this study are significantly limited by the inclusion of some RCTs, such as DEDICATE, which only provide follow-up data up to 1 year. As the authors of the meta-analysis themselves acknowledge, the majority of patients included in their analysis have not yet reached the 5-year follow-up mark. Therefore, the conclusions drawn from this analysis appear premature and inconsistent with the authors’ own stated limitations.
Finally, another methodological consideration is that all the low-risk trials employed non-inferiority designs, which are useful for hypothesis generation but insufficient for establishing equivalence or superiority, especially in unstudied age groups. Using this data to justify expanding TAVI to younger patients below 65 years is a misuse of statistical inference and risks setting clinical decision-making on shaky ground.
Heart Team Decision-Making Must Be Individualized
Age, while a pragmatic marker for life expectancy, cannot replace the nuanced, patient-centered decision-making of a multidisciplinary Heart Team. Clinical guidelines recommend using age thresholds because age is a simple surrogate of life expectancy that can be easily used in clinical practice. So the use of age is a matter of simplicity. However, reducing the TAVI age threshold to below 65 oversimplifies complex decisions about anatomical suitability, comorbidities, patient preferences, long-term and life-time management strategies. Hence, in my opinion, the focus should be on aligning treatment choices with projected longevity and reintervention risks, not just short-term convenience.
Conclusion
TAVI has revolutionized care for many patients with severe AS, but its role in younger, low-risk patients remains uncertain and potentially hazardous. Reducing the age threshold below 65 is neither patient-oriented nor evidence-based. It exposes individuals to long-term risks without proven benefits and shifts the burden of future complications to a population that might otherwise benefit significantly from a surgical approach. Until longer-term data are available and reintervention risks are better understood, clinical prudence must prevail. For now, surgery remains the gold standard for durable aortic valve replacement in younger patients
The views and opinions expressed in this guest blog post are those of the author and do not necessarily reflect the official policy or position of The Society of Thoracic Surgeons.