Thoracic endovascular aortic repair (TEVAR) has become the first-line therapeutic option for a broad spectrum of patients with descending thoracic aortic aneurysms, particularly those at high surgical risk. Reduced perioperative morbidity and mortality, together with faster recovery compared with open surgery, have driven its widespread adoption. In parallel, technological advances in endograft design have enabled the treatment of increasingly complex anatomical configurations.

To minimise the risk of early or late failure, manufacturers recommend strict adherence to the instructions for use (IFU), which define specific anatomical criteria for adequate proximal and distal sealing. In real-world clinical practice, these recommendations are not infrequently exceeded intentionally in order to avoid more invasive open procedures, with clinicians knowingly accepting an additional margin of uncertainty. Unlike the well-documented experience in abdominal aortic aneurysms, the long-term impact of treating thoracic aneurysms outside IFU remains insufficiently explored. The present study addresses this gap through a multicentre experience from tertiary referral centres.

The authors report a retrospective study conducted across four tertiary hospitals, analysing long-term outcomes after TEVAR for degenerative thoracic aortic aneurysms, comparing procedures performed within and outside device IFU. A total of 192 patients were included, of whom 24% were treated outside IFU, predominantly due to proximal sealing zone violations. Five-year overall survival was comparable between groups (61% within IFU vs 66% outside IFU; p = .55). In contrast, freedom from aortic-related reintervention at 5 years was significantly lower in patients treated outside IFU (80% within IFU vs 74% outside IFU; p = .04), suggesting reduced durability when manufacturer recommendations are not respected.

The authors conclude that TEVAR provides favourable long-term results in the treatment of thoracic aortic aneurysms. Selective use of TEVAR outside IFU may be acceptable in carefully selected patients, although it is associated with a higher risk of late reinterventions, particularly in the presence of proximal sealing zone compromise, warranting close surveillance.

COMMENTARY:

This study provides valuable insight into a frequent dilemma in everyday clinical practice: how far it is reasonable to deviate from manufacturer recommendations in order to avoid more aggressive alternatives. The debate is not technical but strategic. Treating outside IFU does not appear to compromise survival, yet it introduces a durability penalty that cannot be overlooked.

A key issue deserving specific reflection is the common confusion between treating outside IFU and treating outside clinical guidelines. These concepts are not interchangeable. International guidelines endorse TEVAR as the first-line treatment for descending thoracic aortic aneurysms when anatomy is favourable, but they do not define sealing criteria with the same level of granularity. These anatomical thresholds are instead delegated to device-specific IFU. Consequently, a procedure may be guideline-compliant while still being performed outside IFU, or vice versa. This distinction is fundamental for interpreting the study findings and for informed decision-making in daily practice.

This discussion aligns with others previously addressed in this blog following publication of the 2024 EACTS/STS guidelines and within the broader context of contemporary management of thoracic aortic disease, where regulatory inertia often coexists with fragile and frequently low-level evidence.

In this regard, we have previously analysed the conceptual differences between European and US approaches to the management of type B aortic dissection, a paradigmatic example of how interpretation of the same evidence can drive either more conservative or more proactive strategies depending on healthcare context.

Going outside IFU does not kill the patient, but it shortens the lifespan of the repair.

Regarding survival, the study reports robust mid- and long-term outcomes. Five-year overall survival exceeded 60% in both groups, with no significant difference. This finding suggests that, at least in terms of vital prognosis, deviation from manufacturer recommendations does not penalise survival, even in a cohort including a higher proportion of elderly patients and complex anatomies.

With respect to late outcomes, freedom from aortic-related reintervention at 5 years was statistically lower in the outside-IFU group. However, despite this statistical significance, the absolute difference between groups was relatively modest. This suggests that, from a clinical standpoint, durability of TEVAR outside IFU may be acceptable in carefully selected patients treated at experienced centres. The risk exists, but it is not evenly distributed.

Proximal sealing emerges as the most critical anatomical determinant of TEVAR durability. Manufacturer recommendations typically require a minimum proximal sealing length of 20–25 mm, a threshold also supported by previous studies and technical consensus statements to reduce the risk of type I endoleak. In the present series, 71% of outside-IFU cases were due to proximal sealing violations, either related to inadequate landing zone location or insufficient proximal neck length. While overall IFU adherence was not associated with increased mortality, proximal sealing violations were linked to a higher risk of late reintervention, reaching statistical significance. This reinforces the notion that not all IFU deviations carry the same clinical weight.

Similarly, in a previous blog entry dedicated to TEVAR for complicated type B dissection, we emphasised that outcomes depend not only on indication but also on very specific technical decisions—part of the surgeon’s mental toolbox—particularly regarding proximal sealing, which may decisively influence long-term durability.

It is also noteworthy that most reinterventions could be managed using endovascular techniques, partially mitigating the impact of the higher failure rate. However, this reassurance only holds in settings with adequate expertise, access to advanced technologies, and an organisational structure capable of ensuring rigorous follow-up.

Several limitations must be acknowledged. The retrospective design inherently limits causal inference. The relatively small number of patients treated outside IFU reduces statistical power, particularly for multivariable analyses. Moreover, patient selection for outside-IFU treatment was necessarily subjective and dependent on individual team judgement, introducing selection bias that is difficult to quantify. Patients with extremely unfavourable anatomy were likely excluded, potentially leading to an overestimation of favourable outcomes outside IFU.

Finally, the study invites an unavoidable reflection on professional responsibility and the legal framework surrounding treatment outside IFU. From a legal and ethical perspective, using devices beyond manufacturer instructions is not inherently unlawful, provided the indication is reasonable, supported by available scientific knowledge, and performed in the patient’s best interest. Nonetheless, this practice requires comprehensive and documented patient information, thorough discussion within the multidisciplinary team, and a clear clinical justification. Going outside IFU is not an automatic prerogative—it is an added burden of responsibility.

Ultimately, rather than serving as a justification to “normalise” TEVAR outside IFU—especially when proximal sealing is compromised—this article should be interpreted as a clinical reminder: individualise indications, communicate transparently with patients, and plan follow-up as an integral component of treatment.

REFERENCE:

Gibello L, Piazza M, Gaggiano A, Maione M, Discalzi A, Squizzato F, et al. Late outcomes of thoracic endovascular aneurysm repair outside versus inside instruction for use. Eur J Cardiothorac Surg. 2025;67(11):ezaf376. doi:10.1093/ejcts/ezaf376.