Single-center retrospective cohort study on long-term outcomes of Zone 1 arch repair with frozen elephant trunk using Frozenix: up to 9.5 years of follow-up
Highlight box
Key findings
• Zone 1 aortic arch repair using the Frozenix Open Stent-Graft showed a 5-year survival rate of 74.5%.
• Acute aortic dissection (AD) cases demonstrated the best long-term outcomes.
• Patients undergoing re-intervention had significantly better survival rates than those who did not.
• The cumulative incidence of re-intervention at 5 years was 24.3%.
What is known and what is new?
• The frozen elephant trunk (FET) technique combines open and endovascular approaches for treating complex aortic arch pathologies.
• Early and mid-term results of FET procedures have been promising.
• This study provides long-term outcomes (up to 9.5 years) of Zone 1 aortic arch repair using the Frozenix Open Stent-Graft in a large cohort of 353 patients.
• It demonstrates the durability and effectiveness of this technique, particularly in acute AD cases.
• The study reveals that timely re-interventions may contribute to improved long-term survival.
What is the implication, and what should change now?
• The Frozenix Open Stent-Graft should be considered a viable option for Zone 1 aortic arch repair, especially in acute AD cases.
• Lifelong surveillance of patients who undergo FET procedures is crucial, as timely re-interventions may improve long-term outcomes.
• Future research should focus on optimizing patient selection criteria and developing strategies to reduce the need for re-interventions while maintaining the survival benefit.
• Cardiovascular surgeons should be prepared to perform complex re-interventions as part of the long-term management of these patients.
Introduction
Background
Zone 1 aortic arch repair is a critical surgical intervention for patients with thoracic aortic diseases such as aortic aneurysm (AA) and aortic dissection (AD). The frozen elephant trunk (FET) technique, which combines open surgical and endovascular procedures, has emerged as a promising approach for complex aortic pathologies. The FET technique involves using a hybrid prosthesis with both a stented and a non-stented portion, allowing for single-stage repair of the aortic arch and the descending aorta. This method aims to stabilize the aortic arch, facilitating subsequent open or endovascular re-intervention procedures if necessary.
The efficacy of the FET technique has been demonstrated in numerous studies, showing significant improvements in early and mid-term postoperative outcomes. The technique has been associated with high survival and acceptable complication rates, particularly for acute ADs (1). The application of the FET technique has shown promising results in managing acute ADs, with studies reporting improved survival outcomes compared to traditional surgical methods. The technique has significantly reduced the risk of late postoperative complications such as false lumen enlargement and the need for reoperation (2).
The Frozenix Open Stent-Graft, a new hybrid graft introduced in the Japanese market in July 2014, has been specifically designed for the FET technique. It has shown promising early outcomes, with good rates of aneurysm exclusion and a low incidence of complications. Studies have reported favorable results with the Frozenix device, highlighting its potential to treat aortic arch diseases effectively. The Frozenix J-graft provided good early outcomes without spinal cord complications or device kinking in patients with aortic arch disease (3).
Rationale and knowledge gap
Despite these advancements, the long-term benefits and potential risks of the FET procedure, including the rates of re-intervention and long-term complications, remain areas of ongoing research and clinical interest. The optimal deployment strategy, particularly regarding the choice of proximal landing zones (Zone 0/1 vs. Zone 2/3) and the impact of patient-specific factors such as comorbidities on outcomes, continue to be debated and investigated (4). There is a need for comprehensive long-term data to understand better the effectiveness and safety of the FET technique, particularly for Zone 1 aortic arch repair.
Objective
This study aims to evaluate the long-term outcomes of Zone 1 aortic arch repair using the Frozenix Open Stent-Graft, focusing on patient survival, complication rates, and re-intervention incidence. By analyzing data from 353 consecutive patients over nearly a decade, this research seeks to provide comprehensive insights into the effectiveness and safety of the FET technique for Zone 1 aortic arch repair. Additionally, it aims to identify key factors that influence long-term outcomes, thereby contributing to optimizing surgical strategies for managing complex aortic pathologies. We present this article in accordance with the STROBE reporting checklist (available at https://jovs.amegroups.com/article/view/10.21037/jovs-24-16/rc).
Methods
Study design
This retrospective cohort study analyzed all patients (total of 353) who underwent Zone 1 aortic arch repair using the Frozenix Open Stent-Graft (Japan Lifeline, Tokyo, Japan) at our center between July 2014 and December 2023 for thoracic AA or AD.
The primary aim was to assess long-term survival outcomes and factors influencing survival rates among different aortic pathologies treated with FET. Primary endpoints included in-hospital mortality, complications, and follow-up survival, while the secondary endpoint was aortic re-intervention.
For accurate assessment of survival and re-intervention outcomes, we excluded patients who experienced early mortality (deaths occurring within 30 days of the procedure). Consequently, survival and re-intervention analyses were conducted on 343 patients who survived beyond this early mortality period (Figure 1).
AD was categorized by onset timing: acute (within 2 weeks), subacute (between 2 weeks and 6 months), and chronic (beyond 6 months), allowing for an understanding of how pathology timing affects long-term outcomes post-intervention.
Surgical procedure
The surgical technique used in this study has been previously described in detail (5).
All patients underwent surgery under general anesthesia via median sternotomy. After systemic heparinization, an 8-mm heparin-bonded expanded polytetrafluoroethylene (ePTFE) graft (GORE PROPATEN Vascular Graft) is anastomosed to the left subclavian artery (LSCA), which is used for selective perfusion during hypothermic circulatory arrest as well as one of the arterial returns if needed for cardiopulmonary bypass.
Arterial return was primarily via the ascending aorta unless diseased, supplemented by the LSCA and/or right subclavian or femoral artery as needed. A single venous cannula was inserted through the right atrium unless bicaval cannulation was required for concomitant procedures.
Cardiopulmonary bypass was initiated, and a vent was placed in the left ventricle via the right upper pulmonary vein. The body was cooled to 25 ℃, and the heart was arrested with the administration of cardioplegia. At 25 ℃, circulatory arrest was initiated with pentobarbital administration.
The aorta was opened, and selective cerebral perfusion was established through balloon-tipped catheters in the brachiocephalic and left carotid arteries and via the graft anastomosed to the LSCA with the root of the LSCA clamped. The aorta was transected at Zone 1, between the brachiocephalic artery and the left common carotid artery, and the Frozenix open stent graft was deployed under transesophageal echocardiography guidance. Balloon angioplasty was performed to ensure distal sealing when necessary.
The graft portion of the Frozenix was trimmed, and a four-branched J-graft neo was anastomosed to the Frozenix and distal stump, followed by re-establishment of lower body perfusion through a side branch. The brachiocephalic and left carotid arteries were reconstructed, and the LSCA was anastomosed to the graft branch. Body rewarming commenced after completing the first two branch anastomoses.
The proximal anastomosis was performed using a standardized technique unless additional procedures were required. Following de-airing and hemostasis, heparin was reversed with protamine, cardiopulmonary bypass was weaned, and the chest was closed in a standard fashion.
Distal landing zone and stent-graft sizing
Preoperative computed tomography (CT) scans guided the determination of the distal landing zone and stent graft size. The distal landing zone was set at one vertebra proximal to the aortic valve level (typically T7–T8). Graft size varied based on aortic pathology.
- Atherosclerotic aneurysm: 110–120% of the external aortic diameter;
- Chronic AD: 100–110% of the true lumen aortic diameter;
- Acute AD: 90% of the total aortic diameter.
The stent graft length was selected to extend 3 cm above the aortic valve level, and the four-branch graft size was based on the aortic diameter between the right innominate artery and the left carotid artery, which increased by 10%. A two-layer sewing technique was used for the distal anastomosis to address the size discrepancies between the grafts and native tissue, reducing the risk of bleeding and pseudoaneurysm formation.
Follow-up
Clinical information, including surgical details, survival, complications, re-intervention, and other relevant data, was collected from medical records. Patients underwent a predischarge CT scan approximately 1 week after the procedure to confirm stent-graft positioning and check for endoleaks. This was followed by annual CT evaluations, with additional scans as needed to assess the impact of the Frozenix device.
Statistical analysis
Continuous variables are presented as means ± standard deviations or medians with interquartile ranges, depending on their distribution. Categorical variables are expressed as frequencies and percentages. Survival analysis was performed using the Kaplan-Meier method, and differences between groups were assessed using the log-rank test. Competing risk analysis evaluated the cumulative incidence of aortic re-intervention, with death as the competing event. Cox proportional hazards regression identified independent predictors of re-intervention and mortality. All statistical analyses were conducted using EZR (Easy R) version 1.54, a graphical user interface for R, with two-sided P values <0.05 considered statistically significant.
Ethical considerations
The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the institutional review board of New Tokyo Hospital (No. 0364), and individual consent for this retrospective analysis was waived.
Results
Patient characteristics
The study included 353 consecutive patients who underwent Zone 1 aortic arch repair using the Frozenix Open Stent-Graft (Japan Lifeline) between July 2014 and December 2023. Patient demographics and clinical characteristics are summarized in Table 1. The mean age of patients was 71.4±11.2 years, with a male predominance (257 males, 96 females). The cohort comprised patients with various thoracic aortic diseases, primarily AA (n=159) and AD (n=194). The follow-up period had a median duration of 2.1 years, with an interquartile range of 0.8 to 4.5 years. The maximum follow-up was 9.5 years, and the minimum was 0.06 years.
Table 1
| Characteristics | Data |
|---|---|
| Total patients | 353 |
| Mean age (years) | 71.4±11.2 |
| Male/female | 257/96 |
| AA | 159 (45.0) |
| AD | 194 (55.0) |
Data are presented as n, mean ± SD, or n (%). AA, aortic aneurysm; AD, aortic dissection.
Outcome of Zone 1 arch replacement using Frozenix
The overall mortality rate was 18.4% (n=65), including a 30-day mortality rate of 2.8% (n=10) and a late mortality rate of 15.6% (n=55) (Table 2). Early deaths were caused by aortic rupture (four cases), low cardiac output syndrome (two cases), abdominal organ malperfusion (one case), extensive cerebral infarction (one case), hypoxic encephalopathy (one case), and sepsis (one case) (Table 3).
Table 2
| Outcomes | Data |
|---|---|
| 30-day mortality | 10 (2.8) |
| Late mortality | 55 (15.6) |
| Stroke† | 35 (9.9) |
| Spinal cord injury‡ | 7 (2.0) |
Data are presented as n (%). †, stroke includes both permanent and transient cases; ‡, spinal cord injury includes both complete and hemi cases.
Table 3
| Cause of death | Early mortality | Total |
|---|---|---|
| Unknown | – | 14 |
| Pneumonia, respiratory failure | – | 10 |
| Aortic rupture | 4 | 9† |
| Cerebral hemorrhage | – | 6 |
| Infection (graft/sepsis/mycotic aneurysm) | – | 5 |
| Renal failure | – | 4 |
| Cerebral infarction, extensive | 1 | 3 |
| Low cardiac output syndrome | 2 | 3 |
| Pulmonary tuberculosis | – | 2 |
| Aortoduodenal fistula | – | 1 |
| Visceral malperfusion | 1 | 1 |
| Hypoxic encephalopathy | 1 | 1 |
| Gastrointestinal bleeding | – | 1 |
| Acute limb ischemia | – | 1 |
| Sepsis (peritonitis, cholecystitis and chronic myeloid lymphoma-related) | 1 | 3 |
| COVID-19 | – | 1 |
| Total | 10 | 65 |
Early mortality is defined as death occurring within 30 days postoperatively. †, among the 9 cases of aortic rupture, 2 occurred preoperatively, while the remaining 7 occurred after the index surgery. COVID-19, coronavirus disease 2019.
The causes of mortality were diverse, including nine cases of aortic rupture (two preoperative and seven postoperative), five cases of infection (e.g., graft infection and persistent sepsis such as mycotic aneurysm), three cases of low cardiac output syndrome, one case of aortoduodenal fistula, one case of visceral malperfusion, one case of hypoxic encephalopathy, six cases of cerebral hemorrhage, three cases of extensive cerebral infarction, 10 cases of pneumonia and respiratory failure, two cases of pulmonary tuberculosis, and four cases of renal failure (Table 3). Additional causes included unknown factors (14 cases), sepsis-related complications (three cases, including peritonitis, cholecystitis, and chronic myeloid leukemia-related sepsis), one case of gastrointestinal bleeding, one case of acute lymphoblastic leukemia (ALL), and one case of coronavirus disease 2019 (COVID-19).
Perioperative morbidities were observed in 9.9% of the patients (n=35) who experienced stroke, including both permanent and transient cases, and in 2.0% of patients (n=7) who developed spinal cord injuries, ranging from complete injuries to hemi-injuries (Table 2).
Aortic pathology (Table 4)
Table 4
| Aortic pathology | Total number of patients | Number of re-intervention (n=65) | |
|---|---|---|---|
| Endovascular (n=39) | Open surgery (n=26) | ||
| AA | 159 | 21 | 5 |
| AD | 194 | 18 | 21 |
| Acute and subacute | 159 | 11 | 17 |
| Type A | 109 | 6† | 12 |
| Type B | 50 | 5 | 5 |
| Chronic | 35 | 7 | 4 |
| Type A | 18 | 2 | 1 |
| Type B | 17 | 5 | 3 |
Aortic re-interventions were performed in 57 patients, totaling 65 aortic re-intervention procedures. AD was defined as acute (≤2 weeks), subacute (2 weeks to 6 months), and chronic
(≥6 months or unknown onset). †, hybrid in 1 patient. AA, aortic aneurysm; AD, aortic dissection.
Among the 353 patients, 159 had AA, and 194 had AD. The AD cases included 159 acute/subacute dissections (109 type A and 50 type B) and 35 chronic dissections (18 type A and 17 type B).
Survival analysis after Zone 1 arch replacement using Frozenix
The overall survival analysis (Figure 2) showed 1-, 3-, and 5-year survival rates of 88.9%, 82.6%, and 76.2%, respectively. Figure 3 illustrates survival by aortic pathology, revealing significant differences among groups (P=0.001). AA had the lowest survival rate, while acute AD had the highest. The graph indicates a clear stratification of survival curves, with acute AD maintaining the best long-term outcomes. These findings highlight the impact of aortic pathology timing on long-term survival outcomes following intervention.
Re-intervention after Zone 1 arch replacement using Frozenix
During the follow-up period, 65 re-interventions comprised 39 endovascular procedures and 26 open surgeries. The cumulative incidence of re-intervention at 1, 3, and 5 years was 8.9%, 15.3%, and 24.3%, respectively (Figure 4).
Type of re-intervention by aortic pathology (Table 4)
Out of the total patient cohort, 65 re-intervention procedures were performed. For patients with AA, 21 endovascular and 5 open surgeries were conducted. The AD group performed 18 endovascular procedures and 21 open surgeries. Specifically, within acute and subacute AD cases, 11 patients underwent endovascular re-interventions, while 17 required open surgeries. There were six endovascular and 12 open procedures for type A dissections, whereas type B dissections had five endovascular and five open surgeries. Chronic AD re-interventions involved seven endovascular and four open surgeries, with type A dissections accounting for two endovascular and one open surgery and type B dissections accounting for five endovascular and three open surgeries.
Indications for re-intervention (Table 5)
Table 5
| Indications | Endovascular (n=39) | Open (n=26) |
|---|---|---|
| DSINE | 13 | 0 |
| Dilatation of descending aorta | ||
| Early diameter progression | 2 | 1 |
| Late diameter progression | 10 [2] | 3 |
| Rupture of descending aorta | 3 [1] | 1 [1] |
| Pseudoaneurysm of ascending aorta | 0 | 2 [1] |
| Pseudoaneurysm of proximal anastomosis | 0 | 2 |
| Re-re-dissection | 0 | 1 |
| Endoleak type 1b | 1 | 0 |
| Endoleak type II | 3 | 0 |
| Migration | 4 [1] | 0 |
| Dilatation of TAAA | 0 | 10 |
| Severe AR (root dissection) | 0 | 3 |
| PVE | 0 | 1 |
| Intended completion | 2 [1] | 0 |
| LSCA dissection | 0 | 1 |
| Rt innominate A stenosis | 1 [1] | 0 |
| Thrombosed AV | 0 | 1 |
Data are presented as total number or total number [number of deaths]. DSINE, distal stent graft-induced new entry; TAAA, thoracoabdominal aortic aneurysm; AR, aortic regurgitation; PVE, prosthetic valve endocarditis; LSCA, left subclavian artery; thrombosed AV, thrombosis of a mechanical aortic valve.
During the follow-up period, 65 re-interventions comprised 39 endovascular procedures and 26 open surgeries. The primary indications for re-intervention were diverse. Dilatation of the descending aorta (late progression) and distal stent-induced new entry (DSINE) were the most common causes for re-intervention, each with 13 cases. These were followed by thoracoabdominal AA (TAAA) dilatation requiring open surgery (10 cases) and endoleaks (eight cases: one type Ib, three type II, and four migrations). Additional causes include rupture of the descending aorta (four cases), pseudoaneurysms (four open surgeries), early diameter progression of the descending aorta (three cases), severe aortic regurgitation due to root dissection (three open surgery), re-dissection (one open surgery), and intended completion (two endovascular cases). Several other causes were recorded in single cases, including re-re-dissection, prosthetic valve endocarditis (PVE), LSCA dissection, right innominate artery stenosis, and thrombosed aortic valve.
Eight patients expired following re-intervention: two from late diameter progression of the descending aorta treated endovascularly, two from descending aortic rupture (one endovascular, one open), one from an ascending aortic pseudoaneurysm treated with open surgery, one from open stent migration treated endovascularly, and one from right innominate artery stenosis after endovascular therapy.
Surgical details of re-intervention
Open surgical re-interventions (n=26) addressed a range of complex aortic pathologies, as detailed in Table 6. The most common indication was dilatation of TAAA (n=10), treated with either TAAA replacement or Y-graft with intimal fenestration (IF). Other procedures included descending aorta replacements for dilatation and rupture, repairs of pseudoaneurysms, re-dissection management, and complex cardiac surgeries for severe aortic regurgitation and thrombosed aortic valve. The diversity of procedures highlights the complexity of re-interventions in aortic surgery. One case of spinal cord injury occurred during TAAA replacement, and one death was reported in a descending aorta rupture case, underscoring the risks associated with these complex procedures.
Table 6
| Indications | Number of cases | Procedure [number] |
|---|---|---|
| Dilatation of descending aorta | ||
| Early diameter progression | 1 | Descending aorta replacement [1] |
| Late diameter progression | 3 | Descending aorta replacement + IF [3] |
| Rupture of descending aorta | 1† | Descending aorta replacement + IF + AK [1] |
| Pseudoaneurysm of ascending aorta | 2† | Ascending aorta repair [2] |
| Pseudoaneurysm of proximal anastomosis | 2 | Proximal anastomosis repair [2] |
| Re-dissection | 1 | Descending aorta replacement + IF [1] |
| Dilatation of TAAA | 10 | TAAA replacement [5]‡ |
| Y-graft + IF [5] | ||
| Severe aortic regurgitation (root dissection) | 3 | Redo-bentall procedure [3] |
| PVE | 1 | Redo-AVR with annuloplasty [1] |
| LSCA dissection | 1 | LSCA-ascending a bypass [1] |
| Thrombosed aortic valve | 1 | Redo AVR + MVR + TAP [1] |
†, one patient died; ‡, one patient experienced spinal cord injury. IF, intimal fenestration; AK, Adamkiewicz artery reconstruction; TAAA, thoracoabdominal aortic aneurysm; PVE, prosthetic valve endocarditis; AVR, aortic valve replacement; LSCA, left subclavian artery; MVR, mitral valve replacement; TAP, tricuspid annuloplasty.
Thirty-nine endovascular re-intervention procedures were performed on 36 patients, with 36 thoracic endovascular aortic repair (TEVAR) procedures completed on 33 patients, as detailed in Table 7. The delivery systems used included Valiant (n=24), Navion (n=5), C-TAG (n=2), Zenith α (n=4), and Relay (n=1). Valiant, C-TAG, and Relay were characterized as outer-frame systems. Navion was described as both outer-frame and low-profile. Zenith α was classified as an inner frame of a top stent and low-profile system. Additionally, two LSCA embolization procedures and one endovsacular aortic repair (EVAR) using Excluder II were performed.
Table 7
| Re-intervention | Procedure (n=39) | Patients (n=36) | Characteristics |
|---|---|---|---|
| TEVAR | 36 | 33 | – |
| Valiant | 24 | – | Outer-frame |
| Navion† | 5 | – | Outer-frame, low-profile |
| C-TAG | 2 | – | Outer-frame |
| Zenith α | 4 | – | Inner-frame of top stent, low-profile |
| Relay | 1 | – | Outer-frame, low-profile |
| LSCA embolization | 2 | – | – |
| EVAR (Excluder II) | 1 | – | – |
†, currently unavailable. TEVAR, thoracic endovascular aortic repair; LSCA, left subclavian artery; EVAR, endovascular aneurysm repair.
Comparison of survival outcomes: re-intervention vs. no re-intervention
The overall survival analysis revealed a significant difference between patients who underwent re-intervention and those who did not (P<0.001). The Kaplan-Meier curve shows higher survival rates for the re-intervention group at all time points (Figure 5). The 1-year survival rate was 98.2% for the re-intervention group vs. 86.9% for the non-intervention group. At 3 years, survival was 96.6% vs. 79.9%, and at 5 years, 93.4% vs. 71.9%, respectively. The figure indicates a consistent survival advantage for patients who received re-intervention, with the difference becoming more pronounced over time.
This study analyzed survival rates in aortic interventions. When comparing open vs. endovascular procedures in re-interventions, Figure 6 showed slightly higher 5-year survival for open procedures (86.2% vs. 77.3%, P=0.24). Figure 7 demonstrated survival by pathology after the first re-intervention, categorizing cases as acute, subacute, or chronic, revealed no significant differences between groups (P=0.71). In chronic ADs (>6 months), a comparison between type A and B showed a 5-year survival of 77.8% for type A and 85.2% for type B. However, this difference was not statistically significant (P=0.94) (Figure 8). These findings suggest comparable outcomes across surgical approaches and pathologies in aortic re-interventions.
Subgroup analysis of chronic dissections (Table 8)
Table 8
| Type of re-intervention | Number of cases | Procedure [number] |
|---|---|---|
| Re-interventions of 18 chronic type A cases | 3 | – |
| Endovascular (2nd staged TEVAR) | 2 | – |
| Open surgery | 1 | Descending aorta replacement [1] |
| Re-interventions of 17 chronic type B cases | 8 | – |
| Endovascular (2nd staged TEVAR) | 5 | Elective completion [3] |
| DSINE [2] | ||
| Open surgery | 3 | Descending aorta replacement + IF + AK [1] |
| Descending aorta replacement + IF [1] | ||
| Redo AVR, MVR, TAP [1] |
TEVAR, thoracic endovascular aortic repair; DSINE, distal stent graft-induced new entry; IF, intimal fenestration; AK, Adamkiewicz artery reconstruction; AVR, aortic valve replacement; MVR, mitral valve replacement; TAP, tricuspid annuloplasty.
Among patients with chronic ADs, we observed distinct patterns of re-intervention. Of 18 chronic type A dissection cases, three required re-intervention: two underwent endovascular procedures (second-stage TEVAR), and one required open surgery for descending aortic replacement. In contrast, among 17 chronic type B dissection cases, eight re-interventions were performed. Of these, five were endovascular procedures (three elective completions and two for DSINE), and three were open surgeries. The open surgeries for type B cases included descending aortic replacement with IF and Adamkiewicz artery reconstruction (one case), descending aortic replacement with IF (one case), and redo aortic valve replacement, mitral valve replacement and tricuspid annuloplasty (one case). These findings suggest a higher re-intervention rate in chronic type B dissections compared to chronic type A, with a notable variety in the complexity of required procedures.
Discussion
Key findings
Our study demonstrates favorable long-term outcomes for Zone 1 aortic arch repair using the Frozenix Open Stent-Graft, with survival rates of 88.9%, 82.6%, and 76.2% at 1, 3, and 5 years, respectively. Notably, patients with acute ADs exhibited superior survival outcomes. The cumulative incidence of re-intervention reached 24.3% at five years, with patients undergoing re-intervention demonstrating significantly improved survival rates compared to those who did not. These findings underscore both the efficacy and safety of the FET technique and emphasize the critical nature of long-term patient management.
Strengths and limitations
The strengths of this study include its large cohort of 353 consecutive patients and the extended follow-up period of nearly a decade. The comprehensive analysis of survival rates, complication rates, and re-intervention incidence provides valuable insights into the long-term outcomes of the FET technique. The study size was determined based on the availability of patients who underwent the procedure at our institution within the specified timeframe.
However, several limitations must be acknowledged. The single-center retrospective design may limit the generalizability of the results. Additionally, ultra-long-term complications beyond 10 years remain to be elucidated, and the impact of patient comorbidities on long-term outcomes warrants further investigation. Potential sources of bias, such as selection and information bias, were addressed by including all consecutive patients and using standardized data collection methods.
Comparison with similar researches
Our findings corroborate previous studies reporting the efficacy of the FET technique, particularly in acute ADs. Yoshitake et al. (2) and Yamamoto et al. (6) observed similar survival advantages using the FET technique for acute type A dissections, suggesting that this approach significantly mitigates the risks associated with complex aortic repairs. In their studies, survival rates at 1, 3, and 5 years were comparable to those observed in our cohort, highlighting the robustness of the FET technique in managing acute dissections.
Complication rates in our study, including a 9.9% incidence of stroke and a 2.0% incidence of spinal cord injury, align with those reported by Hellgren et al. (4) and Tsagakis et al. (7). Hellgren et al. found similar complication profiles in their analysis of a Scandinavian center’s results over 14 years (4). In their multicenter study, Tsagakis et al. also emphasized the importance of meticulous perioperative management to minimize these risks (7).
The high re-intervention rate observed in our study is consistent with findings by Uchida et al. (8), who reported significant survival benefits associated with timely re-interventions. Their study underscores the necessity of ongoing vigilance and follow-up for patients undergoing the FET procedure (8).
Explanations of findings
The superior outcomes in acute AD patients may be attributed to the FET technique’s efficacy in stabilizing the aorta during the acute phase. This stabilization likely prevents the progression of dissection and the development of complications such as false lumen expansion and rupture, which are common in untreated acute dissections (9).
The improved survival rates among patients who underwent re-intervention suggest that timely secondary procedures play a crucial role in long-term management. Re-interventions often address complications such as aortic dilatation and endoleaks, reducing the risk of catastrophic events and improving overall survival (10). This finding is supported by multiple studies, indicating that proactive management of post-surgical complications is essential for improving long-term outcomes (11).
The variation in outcomes across different aortic pathologies underscores the complexity of these diseases and the necessity for tailored surgical approaches. Acute dissections benefit most from the immediate stabilization provided by the FET technique. In contrast, chronic dissections and aneurysms often require more complex and individualized approaches due to their different pathological characteristics (7).
Implications and actions needed
This study showed that the Frozenix Open Stent-Graft could be used to repair Zone 1 aortic arches, especially in cases of acute AD. However, the high re-intervention rate emphasizes the necessity for lifelong surveillance of these patients. Future research should focus on developing more refined patient selection criteria to optimize the benefits of the FET technique while minimizing risks. This includes identifying which patients most likely benefit from the procedure and who may require closer monitoring or early re-intervention (12).
More research needs to be done on long-term complications that last longer than 10 years, finding the best places to use FET, and figuring out how different comorbidities affect patient outcomes. Long-term data will help clarify the durability and safety of the FET technique and guide improvements in surgical practice (10).
We acknowledge the lack of a control group as a limitation of this study. During the study period, Frozenix was the only open stent graft approved for use in our country, and thus all patients underwent treatment using this graft. As a result, we were unable to include a control group treated with different grafts for comparison. This constraint may limit the generalizability of our findings to other graft types.
Cardiovascular surgeons should be prepared to perform complex re-interventions as part of the long-term management of these patients. This may necessitate additional training and expertise in both open and endovascular techniques. Continued advancements in hybrid graft designs and deployment strategies should be pursued further to enhance the safety and effectiveness of the procedure. These improvements may include refinements in stent-graft materials, delivery systems, and branching configurations to accommodate diverse aortic anatomies and pathologies (11). By addressing these areas, the field can work towards improving long-term outcomes and quality of life for patients undergoing Zone 1 aortic arch repair using the FET technique.
Conclusions
In conclusion, Zone 1 aortic arch repair using the Frozenix Open Stent-graft demonstrates promising short- and mid-term outcomes, particularly for acute ADs. The technique’s benefits in reducing late postoperative complications and facilitating re-interventions are well-documented. However, ongoing research is essential to address long-term outcomes, optimal deployment strategies, and patient selection criteria to enhance the effectiveness of this surgical approach further.
Acknowledgments
Funding: None.
Footnote
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jovs.amegroups.com/article/view/10.21037/jovs-24-16/rc
Data Sharing Statement: Available at https://jovs.amegroups.com/article/view/10.21037/jovs-24-16/dss
Peer Review File: Available at https://jovs.amegroups.com/article/view/10.21037/jovs-24-16/prf
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jovs.amegroups.com/article/view/10.21037/jovs-24-16/coif). T.N. serves as an international proctor for Frozenix (Japan Lifeline) receiving an annual consulting fee from the company. The other authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the institutional review board of New Tokyo Hospital (No. 0364), and individual consent for this retrospective analysis was waived.
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
- Tian DH, Ha H, Joshi Y, et al. Long-term outcomes of the frozen elephant trunk procedure: a systematic review. Ann Cardiothorac Surg 2020;9:144-51. [Crossref] [PubMed]
- Yoshitake A, Tochii M, Tokunaga C, et al. Early and long-term results of total arch replacement with the frozen elephant trunk technique for acute type A aortic dissection. Eur J Cardiothorac Surg 2020;58:707-13. [Crossref] [PubMed]
- Morisaki A, Takahashi Y, Fujii H, et al. Early outcomes of the Frozenix J-graft with exclusion of the non-stent part at a single center. J Thorac Dis 2022;14:1031-41. [Crossref] [PubMed]
- Hellgren T, Wanhainen A, Astudillo R, et al. Outcomes of aortic arch repair using the frozen elephant trunk technique: analysis of a Scandinavian center's results over 14 years. J Cardiovasc Surg (Torino) 2023;64:215-23. [Crossref] [PubMed]
- Nakao T, Tsuda S, Kume N, et al. Rapid expansion of the descending aorta following total arch replacement with a FROZENIX-open stent-graft for thoracic aortic aneurysm in a patient with Marfan syndrome: a case report. J Vis Surg 2022;8:25. [Crossref]
- Yamamoto H, Kadohama T, Yamaura G, et al. Total arch repair with frozen elephant trunk using the "zone 0 arch repair" strategy for type A acute aortic dissection. J Thorac Cardiovasc Surg 2020;159:36-45. [Crossref] [PubMed]
- Tsagakis K, Wendt D, Dimitriou AM, et al. The frozen elephant trunk treatment is the operation of choice for all kinds of arch disease. J Cardiovasc Surg (Torino) 2018;59:540-6. [Crossref] [PubMed]
- Uchida N, Katayama A, Tamura K, et al. Long-term results of the frozen elephant trunk technique for extended aortic arch disease. Eur J Cardiothorac Surg 2010;37:1338-45. [Crossref] [PubMed]
- Leone A, Di Marco L, Coppola G, et al. Open distal anastomosis in the frozen elephant trunk technique: initial experiences and preliminary results of arch zone 2 versus arch zone 3†. Eur J Cardiothorac Surg 2019;56:564-71. [Crossref] [PubMed]
- Kreibich M, Kremer J, Vötsch A, et al. Multicentre experience with the frozen elephant trunk technique to treat penetrating aortic ulcers involving the aortic arch. Eur J Cardiothorac Surg 2021;59:1238-44. [Crossref] [PubMed]
- Shrestha M, Bachet J, Bavaria J, et al. Current status and recommendations for use of the frozen elephant trunk technique: a position paper by the Vascular Domain of EACTS. Eur J Cardiothorac Surg 2015;47:759-69. [Crossref] [PubMed]
- Zhang L, Yu C, Yang X, et al. Hybrid and frozen elephant trunk for total arch replacement in DeBakey type I dissection. J Thorac Cardiovasc Surg 2019;158:1285-92. [Crossref] [PubMed]
Cite this article as: Nakao T, Tsuda S, Hoshino S, Ikegaya Y. Single-center retrospective cohort study on long-term outcomes of Zone 1 arch repair with frozen elephant trunk using Frozenix: up to 9.5 years of follow-up. J Vis Surg 2024;10:23.
