Frozen elephant trunk in normothermia without circulatory arrest: initial experience

Introduction

Aortic arch surgery has significantly evolved over the past decades with the introduction of novel techniques and technologies, expanding treatment options and enhancing operative outcomes. However, traditional surgical approaches still require hypothermic circulatory arrest (HCA) and prolonged extracorporeal circulation (ECC), which remain major limitations (1). These factors have been strongly associated with increased mortality and morbidity, posing significant challenges to achieving optimal patient outcomes (1-9). Recently, we introduced a technique that enables the execution of a frozen elephant trunk (FET) under normothermic conditions, eliminating the need for circulatory arrest (10-12). This approach consists of (I) combined femoral and innominate/axillary artery cannulation for ECC arterial return, allowing continuous upper and lower body perfusion; (II) antegrade selective cerebral perfusion (ASCP) with total brain perfusion; (III) retrograde trans-femoral stent graft deployment; and (IV) balloon occlusion following the same route.

Here we present our initial experience in Ancona with this novel approach.

Methods

Study design and patient selection

The present study is a retrospective analysis of outcomes, based on institutional records with prospective data entry. All consecutive patients who underwent FET repair without HCA from September 2019 to January 2025 at the Lancisi Cardiovascular Center in Ancona were included. Patient care was coordinated by a multidisciplinary Aortic Team, involving cardiac surgeons, vascular surgeons and anesthesiologists, all with extensive experience in both open and catheter-based procedures. Cardiac and vascular surgeons operated in tandem in all cases.

Demographic characteristics, medical history, operative outcomes, mid-term results, and imaging data were systematically collected at the time of admission and during follow-up visits. Data were coded according to the Standards of Reporting in Open and Endovascular Aortic Surgery (STORAGE) guidelines, as well as the current guidelines of the European Association for Cardiothoracic Surgery/European Society of Cardiology and the EuroSCORE II model (13-15). All patients underwent preoperative and early postoperative (<30 days) computed tomography angiography (CTA) and echocardiographic examinations. Follow-up CTA was performed at 3 and/or 6 months, 12 months, and annually thereafter, as needed. More frequent CTA surveillance was scheduled for patients with unfavorable aortic remodeling. Follow-up was completed in 100% of cases. In accordance with local ethical standards, the study was notified to the local ethics committee, and all patients provided written informed consent (approved by the Italian Society for Cardiac Surgery) for the use of their anonymized clinical data for research and publication purposes.

Surgical technique

All procedures were performed in a hybrid operating theatre, with patients under general anesthesia. Bilateral radial arterial line pressure monitoring and near-infrared spectroscopy were employed. Transesophageal echocardiography was routinely used. Cerebrospinal fluid drainage was employed in patients at increased risk of spinal cord injury due to extensive aortic coverage or prior distal aortic procedures. The heart and aorta were accessed via median sternotomy in all cases, and the arch vessels were extensively isolated. Both femoral arteries were surgically exposed. After systemic heparinization, arterial inflow for ECC was established and conducted via the innominate/axillary artery and femoral artery using a Y-connector, ensuring continuous perfusion of both the upper and lower body.

The proximal landing zone of the endograft (zone 1, 2 or 3) was identified and marked using multiple large hemoclips. Through the contralateral femoral artery, guided by an extra-stiff guidewire, an appropriate endograft without a free-flow segment was deployed, aligning its proximal edge with the hemoclip markers (Figure 1). A Reliant balloon (Medtronic, USA) was retrogradely advanced into the stent graft via the same femoral artery using a 14-Fr sheath. Under fluoroscopic guidance, the balloon was inflated to simulate aortic clamping, the inflation volume was recorded, the catheter position was marked, and the balloon was then deflated.

Figure 1 Retrograde zone 2 endograft deployment (off-pump). The right femoral and innominate arteries are cannulated for extracorporeal circulation inflow.

Venous drainage was achieved by cannulation of the right atrium, and the left ventricle was vented via the right superior pulmonary vein. ECC was initiated through innominate/axillary artery inflow. The left subclavian artery (LSA) was ligated at its origin and anastomosed distally to an 8-mm vascular graft, which was separately perfused to balance radial artery pressures bilaterally.

After aortic clamping, myocardial protection was achieved via antegrade infusion of cold crystalloid (Custodiol) or Del Nido cardioplegia. The left carotid artery (LCA) was ligated at its origin, cannulated distally, and perfused for ASCP. Following cardioplegic arrest, the innominate artery was proximally clamped, the aortic balloon was inflated with the previously recorded volume, and the ECC femoral line was opened to ensure lower body perfusion. The aortic clamp was removed, and with uninterrupted lower body and cerebral perfusion, the proximal aorta was resected from the sinotubular junction to the endoprosthesis, creating a bloodless operative field.

A four-branched vascular graft was anastomosed to the distal aorta, with internal bites incorporating the endograft and external reinforcement with Teflon felt (Figure 2). The arch graft was clamped, the aortic balloon was deflated, and lower body perfusion was switched from the femoral line to the side branch of the graft to achieve antegrade flow. The proximal anastomosis between the graft and the aortic root was completed, and the heart was reperfused. The three arch vessels were individually anastomosed to the corresponding branches of the graft, completing the aortic reconstruction. The intervention was then completed as usual.

Figure 2 Surgical setup for performing the distal anastomosis without hypothermic circulatory arrest. A combined femoral and innominate artery cannulation for extracorporeal circulation arterial return ensures continuous upper and lower body perfusion, along with antegrade selective cerebral perfusion providing total brain perfusion and retrograde trans-femoral stent graft occlusion using a balloon catheter.

In five patients who had previously undergone thoracic endovascular aortic repair (TEVAR), slightly different approaches were adopted. Patients 1, 3, 11 and 13 presented with a type Ia endoleak, while patient 5 had a type A acute aortic dissection involving the ascending aorta and the proximal arch. In these cases, the same surgical technique was applied without deployment of a new endograft. Instead, a Reliant balloon was retrogradely introduced into the existing stent graft and inflated to achieve endoclamping. ECC was conducted via the innominate artery and femoral artery using a Y-connector, ensuring continuous perfusion of both the upper and lower body. The aorta was resected from the sinotubular junction to the distal end of the existing stent graft, and a four-branched vascular graft was anastomosed, incorporating the stent graft into the distal anastomosis. The procedure then followed the same steps as described above.

In patient 10, who presented with DeBakey type I acute aortic dissection with a large entry tear at the mid-aortic arch, the technique was further modified (10). A single femoral artery access was obtained. The aortic true lumen was catheterized under fluoroscopic and transesophageal echocardiographic guidance. ECC was initiated via cannulation of the non-dissected innominate artery and the right atrium. To address the large entry tear in the mid-aortic arch, the proximal landing zone between the innominate and left carotid arteries (zone 1) was identified and marked using multiple large hemoclips. The LSA was ligated and anastomosed distally to an 8-mm Dacron graft, while the LCA was ligated and cannulated. Both arteries were perfused to enable ASCP. A 24-Fr, 66-cm DrySeal sheath (W.L. Gore, Phoenix, AZ, USA) was introduced through the femoral artery, and with the support of an extra-stiff guidewire, an appropriate endograft without a free-flow segment was cranially advanced and deployed at the marked landing zone. After deployment, the endograft shaft was removed, and the DrySeal sheath was advanced cranially, with its tip positioned securely inside the stent-graft. Through the same sheath, a Reliant balloon was introduced, followed by a 19-Fr arterial cannula connected via a Y-connector to the arterial line supplying the innominate artery. The balloon was inflated to clamp the aorta, and the femoral arterial line was opened, allowing uninterrupted antegrade perfusion of the distal dissected aorta. The intervention then proceeded as described above.

Inclusion criteria and procedural planning

Patient anatomy was carefully evaluated to ensure compatibility with the inclusion criteria. Distal landing zone dimensions and lengths were measured using centerline imaging. Oversizing of the endograft was planned at 15–20% for degenerative aneurysms and ≤5% for acute dissection. The primary inclusion criterion for this procedure was the presence of an adequate distal landing zone for the endograft, enabling retrograde lower body perfusion and ensuring a bloodless operative field during the distal anastomosis. Exclusion criteria included (I) inadequate distal sealing zone; (II) severe aortic tortuosity; (III) absence of viable vascular access options; (IV) extreme aortic diameters; (V) active endocarditis; and (VI) chronic aortic dissection. For patients with acute type A aortic dissection, this approach was used selectively in stable cases, either with a clearly defined primary tear located in the aortic arch (patient 11), or in a patient who had previously undergone TEVAR (patient 5).

Statistical methods

Continuous variables were reported as medians with ranges, and categorical variables were expressed as absolute numbers and percentages. Descriptive statistics were used to summarize demographic characteristics, operative details, perioperative outcomes, and complications. No imputation was performed for missing data. Survival analysis was conducted using the Kaplan-Meier method, with overall survival calculated from the date of surgery to the last follow-up or death. Patients who were alive at the time of last contact were censored. The Kaplan-Meier survival curve was generated to estimate cumulative survival probability over time. Due to the small sample size and exploratory nature of the study, no subgroup comparisons or hypothesis testing were performed. All statistical analyses were conducted using SPSS version 27.0 (IBM Corp., Armonk, NY, USA).

Results

Demographics and operative data

Between September 2019 and January 2025, 23 FET operations without HCA were performed at Polytechnic University of Marche. The median age of the patients was 73 years (range, 60–83 years), and 6 were female. EuroSCORE II ranged from 1.4% to 10% (median, 3.8%). Patients’ characteristics are detailed in Table 1. Surgical indications included degenerative aneurysm in 14 patients, type I endoleak in four, acute dissection in two, chronic penetrating aortic ulcer in two, and Kommerell’s diverticulum in one (Table 2).

All patients underwent total arch replacement with FET construction using a four-branched vascular graft and a stent graft. The stent graft was retrogradely deployed during the same procedure in 18 patients, while five patients (patients 1, 3, 5, 11 and 13) had previously undergone TEVAR. An LCA-LSA bypass was performed in four patients, while a right carotid-right subclavian artery (RCA-RSA) bypass was performed in three patients with an aberrant RSA. In all cases, the LSA or RSA was proximally occluded with a vascular plug. The stent graft coverage level ranged from zone 4 to zone 5. Intraoperative cerebrospinal fluid drainage was used in one patient, while in another case, it was positioned postoperatively due to transient paraparesis. Normothermic or mild hypothermic ECC was applied in 22 patients, while moderate hypothermia was used in one patient with type A acute dissection (patient 10). The median peak lactate level was 1.8 mmol/L (range, 1.0–4.8 mmol/L). Technical success was achieved in 100% of patients. Operative data are summarized in Table 3.

In-hospital outcomes and follow-up

In-hospital outcomes are summarized in Table 4. Within the first 30 days, two patients died: one due to septic shock (patient 12) and another due to postoperative stroke (patient 14). Major complications included temporary dialysis in four patients, stroke in three patients, and respiratory insufficiency in three patients. The median intensive care unit (ICU) and hospital stays were 4 and 11 days, respectively. Postoperative computed tomography scans confirmed successful aortic repair in all cases, with one patient (patient 1) presenting a type II endoleak, which was initially managed conservatively.

Follow-up data are detailed in Table 5. The follow-up period ranged from 1 to 63 months (median, 27 months). Overall survival at 1, 2 and 3 years was 86.1%±7.5%, 75.6%±9.6%, and 69.8%±10.4%, respectively (Figure 3). Four patients died during follow-up due to myocardial infarction (n=2), sudden death (n=1), or an unknown cause (n=1). Two patients experienced an ischemic stroke. A distal aortic reintervention was performed in three patients: two underwent TEVAR for a type Ib endoleak, while one patient with a type II endoleak (patient 1) underwent percutaneous embolization and surgical ligation of the intercostal arteries.

Figure 3 Kaplan-Meier survival curve. pts, patients.

Discussion

HCA remains the principal limitation of aortic arch surgery, as it is associated with increased risks of neurological injury, organ dysfunction, and prolonged recovery (1-9). Recent evidence indicates that even short durations of HCA (<20 minutes) result in cognitive deficits in 40% of patients, including those receiving ASCP, with documented neuroimaging lesions (1). This confirms that no duration of HCA can be considered completely safe, as even short periods may result in brain injury. Therefore, research and technological advancements should focus on developing techniques that eliminate the need for HCA during arch repair.

Surgical technique and indications

At our center in Ancona, through close collaboration between cardiac and vascular surgeons within the Aortic Team, we have developed a technique that enables FET procedures to be performed without circulatory arrest, with normothermia maintained throughout. By combining surgical and endovascular techniques, this approach ensures continuous cerebral and systemic perfusion, potentially addressing longstanding challenges in aortic arch surgery. The ideal candidates for this technique are patients with degenerative aneurysms or penetrating aortic ulcers who have an adequate distal landing zone for proper stent graft sealing. Indeed, this approach is not applicable to patients with chronic dissections and is only suitable for selected acute dissection cases with favorable anatomy. In our experience, two acute dissection patients were treated: patient 5, who had previously undergone TEVAR prior to the acute dissection, and patient 10, who had a single primary tear in the mid-aortic arch and was clinically stable at presentation. Additional limitations of this technique include the increased complexity and bleeding risk associated with the distal anastomosis to the endograft, as well as its more technically demanding nature compared to conventional FET. This operation requires advanced hybrid operating room facilities and significant surgical expertise in both open and endovascular procedures, which may not be universally available. Nevertheless, we achieved a 100% technical success rate in this series, supporting the feasibility of our technique.

Preliminary results

Given the complexity and high-risk profile of the study cohort, the observed outcomes were satisfactory, providing preliminary evidence of the safety and effectiveness of the technique. In the present series, two patients died during the hospital stay (patients 12 and 14). Patient 12 was a high-risk female with severe peripheral vasculopathy, advanced renal failure (stage IIIb) and severe chronic obstructive pulmonary disease. Given her complex vascular status, which was anatomically unfeasible for total endovascular arch repair, a staged hybrid repair was performed. In the first stage, she underwent zone 2 TEVAR via left common iliac artery (LCIA) access, along with an LCA-LSA bypass, endovascular LSA occlusion, and an LCIA-left common femoral artery (LCFA) bypass. In the second stage, FET construction was completed using the previously created LCIA-LCFA bypass as the arterial inflow site for ECC. Although the procedure was technically successful, postoperative recovery was complicated. After initial extubation, she developed pneumonia, respiratory insufficiency and acute kidney injury on postoperative day four, requiring reintubation, tracheostomy and dialysis. Despite intensive care support, she ultimately died due to septic shock. The second in-hospital death (patient 14) was an elderly male (82 years) who suffered, during uneventful post-operative course, a major stroke four days after the operation.

Spinal cord injury is a well-documented complication of conventional FET, with its risk increasing proportionally to the extent of aortic coverage (16). In our series, despite the extensive stent graft coverage, no cases of spinal cord injury were observed. This finding suggests a potential protective advantage of our technique over traditional approaches, likely due to the continuous body perfusion maintained throughout the procedure. Supporting this hypothesis, a key observation of our study was that intraoperative lactate levels remained within near-normal values in all patients (Table 3), indicating preserved perfusion of both the upper and lower body.

Indeed, unlike previously reported techniques aimed at reducing HCA (17), our approach completely eliminates the need for circulatory arrest and simultaneously maintains normothermic ECC, ensuring a bloodless and maneuverable operative field. This is achieved through retrograde balloon advancement into the stent graft for aortic clamping, rather than an antegrade approach. We believe this could improve patient outcomes by reducing ischemia-reperfusion injury during the operation. Nevertheless, a larger cohort is required to validate this hypothesis.

Limitations

This study was conducted as a single-center, retrospective analysis, limiting its external validity. The absence of control cases further restricts the ability to draw definitive comparisons between this technique and traditional methods involving HCA. The relatively small patient cohort reduces the statistical power of the study and may not capture the full range of potential complications or long-term outcomes. Our series includes a highly selective population, with patients chosen based on anatomical compatibility and clinical stability, potentially skewing the results toward more favorable outcomes.

Conclusions

Normothermic FET without circulatory arrest represents a promising evolution in aortic arch surgery. Our initial experience demonstrated a high technical success rate and favorable clinical outcomes in selected patients. However, larger cohort studies are needed to validate these findings and assess the broader applicability of the technique.

Acknowledgments

None.

Footnote

Funding: None.

Conflicts of Interest: The authors have no conflicts of interest to declare.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Hughes GC, Chen EP, Browndyke JN, et al. Neurocognitive Dysfunction After Short (<20 Minutes) Duration Hypothermic Circulatory Arrest. Ann Thorac Surg 2025;119:343-50. [Crossref] [PubMed]
2. Nakamura K, Onitsuka T, Yano M, et al. Risk factor analysis for ascending aorta and aortic arch repair using selective cerebral perfusion with open technique: role of open-stent graft placement. J Cardiovasc Surg (Torino) 2006;47:659-65.
3. Khaladj N, Shrestha M, Meck S, et al. Hypothermic circulatory arrest with selective antegrade cerebral perfusion in ascending aortic and aortic arch surgery: a risk factor analysis for adverse outcome in 501 patients. J Thorac Cardiovasc Surg 2008;135:908-14. [Crossref] [PubMed]
4. Di Eusanio M, Berretta P, Cefarelli M, et al. Total Arch Replacement Versus More Conservative Management in Type A Acute Aortic Dissection. Ann Thorac Surg 2015;100:88-94. [Crossref] [PubMed]
5. Mousavizadeh M, Daliri M, Aljadayel HA, et al. Hypothermic circulatory arrest time affects neurological outcomes of frozen elephant trunk for acute type A aortic dissection: A systematic review and meta-analysis. J Card Surg 2021;36:3337-51. [Crossref] [PubMed]
6. Czerny M, Krähenbühl E, Reineke D, et al. Mortality and neurologic injury after surgical repair with hypothermic circulatory arrest in acute and chronic proximal thoracic aortic pathology: effect of age on outcome. Circulation 2011;124:1407-13. [Crossref] [PubMed]
7. Svensson LG, Crawford ES, Hess KR, et al. Deep hypothermia with circulatory arrest. Determinants of stroke and early mortality in 656 patients. J Thorac Cardiovasc Surg 1993;106:19-28; discussion 28-31.
8. Cao L, Guo X, Jia Y, et al. Effect of Deep Hypothermic Circulatory Arrest Versus Moderate Hypothermic Circulatory Arrest in Aortic Arch Surgery on Postoperative Renal Function: A Systematic Review and Meta-Analysis. J Am Heart Assoc 2020;9:e017939. [Crossref] [PubMed]
9. Tian DH, Wan B, Di Eusanio M, et al. A systematic review and meta-analysis on the safety and efficacy of the frozen elephant trunk technique in aortic arch surgery. Ann Cardiothorac Surg 2013;2:581-91. [Crossref] [PubMed]
10. Di Eusanio M, Gatta E. Frozen Elephant Trunk Without Circulatory Arrest in Acute Aortic Dissection. Ann Thorac Surg 2021;112:e143-5. [Crossref] [PubMed]
11. Di Eusanio M, Cefarelli M, Alfonsi J, et al. Arch Surgery for Type Ia Endoleak: How to Remain Normothermic and Avoid Circulatory Arrest. Ann Thorac Surg 2020;110:e139-41. [Crossref] [PubMed]
12. Di Eusanio M, Cefarelli M, Alfonsi J, et al. Normothermic frozen elephant trunk surgery without circulatory arrest: how we do it in Ancona. Ann Cardiothorac Surg 2020;9:244-5. [Crossref] [PubMed]
13. Rylski B, Pacini D, Beyersdorf F, et al. Standards of reporting in open and endovascular aortic surgery (STORAGE guidelines). Eur J Cardiothorac Surg 2019;56:10-20. [Crossref] [PubMed]
14. Czerny M, Grabenwöger M, Berger T, et al. EACTS/STS Guidelines for diagnosing and treating acute and chronic syndromes of the aortic organ. Eur J Cardiothorac Surg 2024;65:ezad426. Erratum in: Eur J Cardiothorac Surg 2024;65:ezae235. [Crossref] [PubMed]
15. Nashef SA, Roques F, Sharples LD, et al. EuroSCORE II. Eur J Cardiothorac Surg 2012;41:734-44; discussion 744-5. [Crossref] [PubMed]
16. Preventza O, Liao JL, Olive JK, et al. Neurologic complications after the frozen elephant trunk procedure: A meta-analysis of more than 3000 patients. J Thorac Cardiovasc Surg 2020;160:20-33.e4. [Crossref] [PubMed]
17. Malvindi PG, Alfonsi J, Berretta P, et al. Normothermic frozen elephant trunk: our experience and literature review. Cardiovasc Diagn Ther 2022;12:262-71. [Crossref] [PubMed]