Regeneration of Nonhuman Primate Hearts With Human Induced Pluripotent Stem Cell-Derived Cardiac Spheroids.

BACKGROUND: The clinical application of human induced pluripotent stem cell-derived cardiomyocytes (CMs) for cardiac repair commenced with the epicardial delivery of engineered cardiac tissue; however, the feasibility of the direct delivery of human induced pluripotent stem cell-derived CMs into the cardiac muscle layer, which has reportedly induced electrical integration, is unclear because of concerns about poor engraftment of CMs and posttransplant arrhythmias. Thus, in this study, we prepared purified human induced pluripotent stem cell-derived cardiac spheroids (hiPSC-CSs) and investigated whether their direct injection could regenerate infarcted nonhuman primate hearts. METHODS: We performed 2 separate experiments to explore the appropriate number of human induced pluripotent stem cell-derived CMs. In the first experiment, 10 cynomolgus monkeys were subjected to myocardial infarction 2 weeks before transplantation and were designated as recipients of hiPSC-CSs containing 2×107 CMs or the vehicle. The animals were euthanized 12 weeks after transplantation for histological analysis, and cardiac function and arrhythmia were monitored during the observational period. In the second study, we repeated the equivalent transplantation study using more CMs (6×107 CMs). RESULTS: Recipients of hiPSC-CSs containing 2×107 CMs showed limited CM grafts and transient increases in fractional shortening compared with those of the vehicle (fractional shortening at 4 weeks after transplantation: 26.2±2.1%; 19.3±1.8%; P<0.05), with a low incidence of posttransplant arrhythmia. Transplantation of increased dose of CMs resulted in significantly greater engraftment and long-term contractile benefits (fractional shortening at 12 weeks after transplantation: 22.5±1.0%; 16.6±1.1%; P<0.01, left ventricular ejection fraction at 12 weeks after transplantation: 49.0±1.4%; 36.3±2.9%; P<0.01). The incidence of posttransplant arrhythmia slightly increased in recipients of hiPSC-CSs containing 6×107 CMs. CONCLUSIONS: We demonstrated that direct injection of hiPSC-CSs restores the contractile functions of injured primate hearts with an acceptable risk of posttransplant arrhythmia. Although the mechanism for the functional benefits is not fully elucidated, these findings provide a strong rationale for conducting clinical trials using the equivalent CM products.

Intracoronary transplantation of pluripotent stem cell-derived cardiomyocytes: Inefficient procedure for cardiac regeneration.

Advances in stem cell biology have facilitated cardiac regeneration, and many animal studies and several initial clinical trials have been conducted using human pluripotent stem cell-derived cardiomyocytes (PSC-CMs). Most preclinical and clinical studies have typically transplanted PSC-CMs via the following two distinct approaches: direct intramyocardial injection or epicardial delivery of engineered heart tissue. Both approaches present common disadvantages, including a mandatory thoracotomy and poor engraftment. Furthermore, a standard transplantation approach has yet to be established. In this study, we tested the feasibility of performing intracoronary administration of PSC-CMs based on a commonly used method of transplanting somatic stem cells. Six male cynomolgus monkeys underwent intracoronary administration of dispersed human PSC-CMs or PSC-CM aggregates, which are called cardiac spheroids, with multiple cell dosages. The recipient animals were sacrificed at 4 weeks post-transplantation for histological analysis. Intracoronary administration of dispersed human PSC-CMs in the cynomolgus monkeys did not lead to coronary embolism or graft survival. Although the transplanted cardiac spheroids became partially engrafted, they also induced scar formation due to cardiac ischemic injury. Cardiac engraftment and scar formation were reasonably consistent with the spheroid size or cell dosage. These findings indicate that intracoronary transplantation of PSC-CMs is an inefficient therapeutic approach.

Central extracorporeal membrane oxygenation with left-ventricular vent for fulminant myocarditis: a retrospective study.

PURPOSE: Fulminant myocarditis presents as acute severe heart failure and requires mechanical cardiocirculatory support. Left-ventricular (LV) decompression is necessary for the successful recovery of these patients. This retrospective study aimed to evaluate the functional outcomes of providing central extracorporeal membrane oxygenation (ECMO) with LV decompression for the treatment of refractory fulminant myocarditis. METHODS: Between January 2015 and February 2021, seven consecutive fulminant myocarditis patients (mean age: 41.1 ± 26.1 years) received central ECMO support with transapical LV decompression, with an 18 French cannula integrated into the ECMO circuit in a Y-fashion. The baseline characteristics and postoperative outcomes of the patients were collected. RESULTS: On admission, all patients received prior peripheral ECMO, and 85.7% (6/7) of patients received prior intra-aortic balloon pumping. However, all patients had refractory cardiogenic shock that failed prior to decompression. Six patients recovered successfully after a mean ECMO support of 20.0 ± 11.5 days and five patients had no recurrence of cardiac decompensation. The mean ICU and mean hospital stays were 36.7 ± 23.5 days and 60.6 ± 24.9 days, respectively. Hospital mortality was 28.6% (2/7). Two patients died due to sepsis and stroke during hospitalization. CONCLUSIONS: Central ECMO with an LV vent was effective for fulminant myocarditis refractory to percutaneous cardiopulmonary support therapy and other therapies.

Cardiac Regeneration Using Pluripotent Stem Cells and Controlling Immune Responses.

Pluripotent stem cell (PSC)-derived cardiomyocytes are a promising source of cells in myocardial regeneration therapy for end-stage heart failure. Because most previous reports have focussed on xenotransplantation models using immunocompromised animals, studies on immune rejection in allogeneic transplantation models are needed for preclinical and clinical applications. Human leukocyte antigen (HLA) plays an important role in allogeneic transplantation, and cell bank projects are currently underway worldwide to stock induced pluripotent stem cells (iPSCs) generated from healthy individuals with homozygous HLA haplotypes. However, it is difficult to stock iPSCs that match the entire population in these cell banks; thus, several groups have produced hypoimmunogenic PSCs by knocking out HLA. These HLA-knockout PSCs were able to avoid rejection by T cells but still suffered rejection by natural killer (NK) cells caused by 'missing self-recognition'. Recent studies have attempted to generate hypoimmunogenic PSCs with gene editing to inhibit NK cell activation. Regenerative medicine using autologous iPSCs can be an ideal transplantation therapy, but, currently, there are major hurdles to its practical application. Hopefully, further research will resolve these issues. This review provides an overview of the current understanding and progress in this field.

Therapeutic window for obtaining favorable remodeling after thoracic endovascular aortic repair of type B aortic dissection.

OBJECTIVE: The purpose of the present study was to determine the most appropriate timing for thoracic endovascular aortic repair (TEVAR) of type B aortic dissection (TBAD) in terms of remodeling of the aorta. METHODS: A total of 41 patients who had undergone TEVAR for the treatment of aortic dissection were included in the present study. The patients were divided into two groups: those who had undergone TEVAR in the acute or subacute phase (group A) and those who had undergone TEVAR in the chronic phase (group B). The indications for TEVAR as the treatment of TBAD were the presence of aortic rupture or malperfusion of the aortic branches, a maximum aortic diameter of ≥40 mm on the initial diagnostic computed tomography scan, and/or expansion of the aorta of ≥5 mm within 3 months for acute and subacute TBAD. The indication was a maximum aortic diameter of ≥50 mm or expansion of the aorta of ≥5 mm within 1 year for chronic TBAD. The diameters of the aorta, true lumen, and false lumen were measured at the level of the most dilated part of the descending aorta (level M) and at the diaphragm (level D) on the computed tomography scan obtained before TEVAR and at the 2-year follow-up examination. RESULTS: The median interval between TEVAR and the onset of TBAD was 0.2 month (interquartile range, 0.03-0.7 month) in group A (n = 21) and 32 months (interquartile range, 4.7-35.2 months) in group B (n = 20). Except for the aortic diameter at level D in group B, favorable remodeling was obtained at both levels in both groups. The diameter change ratio of the aorta at level D was significantly greater in group A than in group B (P = .02). Receiver operating characteristic curve analysis of the interval for a significant decrease in the aortic diameter at level D yielded 4.2 months as the optimal threshold for performing TEVAR (area under the curve, 0.859; 95% confidence interval, 0.7-1.0). CONCLUSIONS: TEVAR for TBAD will result in favorable outcomes, irrespective of the timing of the procedure. However, it might be more effective to perform TEVAR within 4.2 months of the onset of TBAD, provided that the TEVAR procedure can be performed safely.

[Successful Removal of Intrapericardial Needle using Needle Guidance System].

A 41-year-old man stuck himself with needle through his pericardium during suicide attempt. Chest radiography revealed several needles in the bilateral lung fields as well. Computed tomography (CT) and echocardiography showed massive pericardial effusion and a needle penetrating the pericardium. The patient was initially treated conservatively, including pericardial drainage, and, seven days later, we removed the needle using syngo Needle Guidance in hybrid operating room. The length of skin incision was only 2 cm, and the postoperative course was uneventful. No previous studies, to the best of our knowledge, have shown the use of syngo Needle Guidance to remove a needle in the pericardial cavity. This surgical procedure is minimally invasive for the patient.

Impact of the Frozen Elephant Trunk Technique on Total Aortic Arch Replacement.

BACKGROUND: The frozen elephant trunk (FET) technique can facilitate the distal anastomosis of total arch replacement (TAR); therefore, the technique is increasingly being used in TAR cases. However, identifying suitable patients remains controversial. This study analyzes the outcome of TAR using FET and clarifies the indications for using FET. METHODS: Patients who underwent TAR between January 2008 and December 2018 were enrolled and divided into 2 groups: that is, patients treated with conventional TAR (cTAR group, n = 39) and those treated with TAR using FET (TAR-FET group, n = 76). Early and late outcomes were compared. RESULTS: The mean operation time was significantly shorter in the TAR-FET group (447.0 ± 82.1 min) than in the cTAR group (509.4 ± 123.9 min) (P < 0.01). Likewise, circulatory arrest time was significantly shorter in the TAR-FET group (29.0 ± 7.8 min) than in the cTAR group (64.2 ± 20.2 min) (P < 0.001). Postoperative renal function tended to be preserved in the TAR-FET group. Recurrent nerve palsy was less frequent in the TAR-FET group (9.2%) compared with the cTAR group (25.6%) (P < 0.05). Patients with chronic aortic dissection tended to undergo reintervention more frequently following TAR using the FET technique. CONCLUSIONS: The FET technique contributed to save operation and circulatory arrest times during TAR and seemed less invasive in terms of renal function and less-frequent recurrent nerve palsy. Considering posttreatment reintervention, however, care should be taken in its application to chronic aortic dissection.

Thoracic endovascular aortic repair for retrograde type A aortic dissection.

OBJECTIVE: The efficacy of thoracic endovascular aortic repair (TEVAR) for retrograde type A aortic dissection (r-TAAD) with the entry tear in the descending aorta has not been clarified. METHODS: The medical records of 31 patients who underwent TEVAR for r-TAAD at three institutions between May 1997 and January 2016 were retrospectively reviewed. RESULTS: The mean age of the patients (30 men and 1 woman) was 64 ± 11 years. The entry tear was located in the descending thoracic aorta in all patients. Seven patients (23%) had dissection-related complications. The false lumen of the ascending aorta was patent in 13 patients (42%) and thrombosed in 18 (58%). The maximum diameter of the ascending aorta was 45 ± 4 mm. TEVAR was performed in the acute phase in 24 patients (77%) and in the subacute phase in 7 (23%). Only one patient (3%) died of aortic rupture within 30 days after TEVAR. Early aorta-related adverse events were observed in eight patients (26%), of whom five underwent additional interventions. The mean follow-up period was 99 ± 69 months. There were no late aorta-related deaths, although five patients died of other causes during follow-up. Overall survival rates at 1 year, 5 years, and 10 years were 97%, 93%, and 80%, respectively. Late aorta-related adverse events were observed in seven patients (23%), of whom five underwent additional interventions. Aorta-related event-free survival rates at 1 year, 5 years, and 10 years were 58%, 58%, and 51%, respectively. CONCLUSIONS: TEVAR for r-TAAD seems promising in terms of survival. However, the incidence of postoperative aorta-related adverse events is not negligible, so careful selection of patients is important. In addition, close follow-up is mandatory after TEVAR to avoid catastrophic consequences.

Treatment of Infected Aneurysm with Combined Endovascular Aneurysm Repair and Abscess Drainage.

PURPOSE: To evaluate the clinical utility of combination therapy with endovascular aneurysm repair (EVAR) and abscess drainage for the treatment of infected aneurysms. MATERIALS AND METHODS: Between July 2009 and May 2015, 8 patients underwent combination therapy with EVAR and abscess drainage. There were 5 men and 3 women, with a mean age of 75 years ± 7. Aneurysms were of the thoracic aorta in 5 patients, the abdominal aorta in 2, and the internal iliac artery in 1. Four patients had concurrent infection, including pyelonephritis in 2, pelvic abscess in 1, and suppurative knee arthritis in 1. Three patients had ruptured aneurysms. Abscess drainage was performed percutaneously under computed tomographic guidance in 5 patients, thoracoscopic guidance in 2, and both in 1. RESULTS: Six patients (75%) were discharged without additional intervention except for antibiotic therapy, and the other 2 patients (25%) underwent open repair to control infection and to repair endoleak, respectively. There were no in-hospital deaths. During the mean follow-up period of 48 months ± 22, all patients were alive except for 1 patient who died of recurrence of rectal cancer at 51 months. There were no aorta- or artery-related adverse events. Overall survival rates at 1 and 5 years were 100% and 80%, respectively. Aneurysm-related event-free rates at 1 and 5 years were 75%. CONCLUSIONS: Combination therapy with EVAR and abscess drainage for the treatment of infected aneurysms seems to be a promising strategy as an alternative or "bridge" to open surgery.

Parallel placement of Excluder legs for treatment of type IIIb endoleaks caused by fabric tear after endovascular aneurysm repair.

A total of 576 patients underwent endovascular aneurysm repair using main body devices for treatment of abdominal aortic aneurysms or iliac artery aneurysms. During follow-up, type IIIb endoleaks caused by fabric tear occurred in six patients (1.0% [6/576]). The device used was Zenith (Cook Medical, Bloomington, Ind) in five cases and Talent (Medtronic, Santa Rosa, Calif) in one case. All endoleaks were close to the flow divider of the main body devices. The distance between the lower renal artery and the top end of the contralateral leg was 53 ± 14 mm. Bell-bottom-shaped Excluder (W. L. Gore & Associates, Flagstaff, Ariz) legs were placed parallel from the top of the main body device through both legs to treat these endoleaks. In two patients, coil embolization was required to treat gutter endoleaks. Postoperative computed tomography showed the obliteration of type IIIb endoleaks in all patients. Our technique may be an acceptable method for treatment of type IIIb endoleaks, especially when they occur near the flow divider.

Treatment of Infected Aneurysms of the Abdominal Aorta and Iliac Artery with Endovascular Aneurysm Repair and Percutaneous Drainage.

Infected aneurysm remains one of the most challenging diseases for vascular surgeons. We describe the successful treatment of 2 cases of infected aneurysms with endovascular aneurysm repair and percutaneous computed tomography-guided drainage. This strategy may be an effective alternative to open surgical repair in selected patients.

Treatment Strategies for Improving the Surgical Outcomes of Ruptured Abdominal Aortic Aneurysm: Single-Center Experience in Japan.

Objective: We aimed to examine the surgical outcomes of ruptured abdominal aortic aneurysm cases at our hospital and considered strategies for improvement. Material and Methods: We examined the preoperative characteristics of hospital mortality, postoperative complications, and long-term outcomes of 91 surgical cases of ruptured abdominal aortic aneurysm performed between January 2009 and December 2020 at our hospital. Results: Of the 91 cases, 24 died at the hospital (mortality, 26.3%). Mortality was mostly due to hemorrhage/disseminated intravascular coagulation and intestinal necrosis. Ten patients required preoperative aortic clamp by thoracotomy or insertion of intra-aortic balloon occlusion, and eight of them died. Ten patients required open abdominal management due to abdominal compartment syndrome, and five of them died. There was no significant difference between the two groups in terms of the long-term results of the open repair and abdominal endovascular aneurysm repair (EVAR). Conclusion: To improve the surgical outcomes of ruptured abdominal aortic aneurysms, it is necessary to start surgery immediately. Therefore, the choice of surgical method (open surgery or EVAR) should be based on the resources and discretion of the hospital. To prevent postoperative intestinal necrosis, risk factors for acute compartment syndrome should be considered, and open abdominal management should be introduced.

Usefulness of 18F-FDG PET/computed tomography in differentiating between subacute and chronic aortic dissection: initial investigation.

OBJECTIVES: In the selection of thoracic endovascular repair for aortic dissection (AD), it is important to distinguish between the subacute and chronic phases, but there is no reliable way to distinguish between them in patients with unknown onset of AD. The purpose of this study was to assess the diagnostic performance of 2-[18F] fluoro-2-deoxy-d-glucose (18F-FDG)-PET/computed tomography (PET/CT) for discriminating subacute AD from chronic AD. METHODS: Thirteen patients with AD who were medically treated and followed up for 6 months were studied. 18F-FDG PET/CT images were obtained for each patient in the subacute phase (the first scan) and at 6 months (the second scan) after the onset. Target-to-background ratio (TBR) was measured as the maximum standardized uptake value (SUV) in the dissected aortic wall divided by blood pool SUV. RESULTS: TBR was significantly higher in the first scan (mean ± SD, 1.97 ± 0.32) than in the second scan (1.69 ± 0.29, P = 0.007). The area under the receiver operating characteristic curve of TBR for discriminating subacute AD from chronic AD was 0.76. With a threshold of 1.74, the TBR showed the sensitivity, specificity, and positive and negative predictive value of 85%, 69%, 73%, and 82%, respectively, for the discrimination of subacute AD from chronic AD. CONCLUSION: Metabolic assessment of dissected aortic wall by 18F-FDG PET/CT is useful in differentiating between subacute and chronic AD and can provide important information in determining the appropriate indication for treatment for patients with AD of unknown onset.

Utility of Psoas Muscle Area in Selecting Older Patients Feasible for Thoracic Endovascular Aortic Repair.

BACKGROUND: The impact of psoas muscle area on overall survival is unknown for older patients undergoing elective thoracic endovascular aortic repair. METHODS: We retrospectively reviewed 105 patients aged 75 years or more who underwent elective thoracic endovascular aortic repair for descending thoracic aortic aneurysm between January 2010 and December 2019. Psoas muscle area was measured at the L3 level with preoperative computed tomography and adjusted by height squared to derive psoas muscle mass index. The patients were stratified into two groups, sarcopenia and nonsarcopenia. sarcopenia was defined as a psoas muscle mass index less than 5.40 cm2/m2 for men and less than 3.56 cm2/m2 for women. The overall survival was compared with the age- and sex-matched general population using the one-sample log rank test. The propensity score adjusted Cox proportional hazards model was applied to determine the hazard ratio for all-cause mortality. RESULTS: Twenty-three patients died during the follow-up period (median, 3 years). Thirty-eight patients (36%) were classified as sarcopenia. The 5-year overall survival rate was 46% (95% confidence interval, 29% to 73%) for sarcopenia and 84% (95% confidence interval, 74% to 94%) for nonsarcopenia. The overall survival was significantly lower in the sarcopenia group than in its matched general population (P = .004), whereas no statistically significant difference in overall survival was found between the nonsarcopenia group and its matched general population (P = .417). Sarcopenia was an independent risk factor for all-cause mortality (adjusted hazard ratio 2.64; 95% confidence interval, 1.02 to 6.82; P = .045). CONCLUSIONS: Psoas muscle mass index may be a good predictor of mortality among older patients undergoing elective thoracic endovascular aortic repair for descending thoracic aortic aneurysm.

Intimal Sarcoma after Endovascular Abdominal Aortic Aneurysm Repair.

A 72-year-old man, who was treated 10 years earlier with endovascular aortic aneurysm repair, presented with a fever. Considering the concern of stent graft infection, the patient was treated with antibiotics, but his condition did not improve. He underwent stent graft resection and reconstruction with a Dacron graft. Pathological analysis of the aortic wall and computed tomography revealed recurrent intimal sarcoma, and the patient underwent resurgery. During follow-up, he underwent two additional resections for local recurrence, but he died 17 months later. Our results suggest that intimal sarcoma should be considered during the follow-up after endovascular aortic aneurysm repair.

[Endovascular therapy of abdominal aortic aneurysms: present and future status in Japan].

Since the Ministry of Health, Labor, and Welfare approved Cook's Zenith AAA in 2006, endovascular repair of abdominal aortic aneurysms (AAAs) has become a widespread, acceptable alternative to traditional surgical intervention in Japan, although it lagged far behind Western countries in adopting this technique. The number of patients who undergo endovascular aortic aneurysm repair (EVAR) is now 3,000 annually and it is expected to exceed 4,000 in the near future, which means that more than half of patients with abdominal aortic or iliac arterial aneurysms will undergo EVAR. A paradigm shift has thus emerged in the field of AAA repair, in which surgical graft replacement was the gold standard for more than 50 years. EVAR is now under the strict control of the Japanese Committee for Stentgraft Management (JACSM), which was established by 10 societies related to endovascular therapy. This appears to be one of the reasons why the outcomes of EVAR in Japan are markedly better compared with those in other countries. EVAR has made it possible to treat high-risk patients because it does not require laparotomy. Therefore, patients who would have been observed without intervention in the past can now benefit from EVAR. In Japan, an extremely aged society, endovascular repair will become a much more common measure for the treatment of patients with AAA.

Strategies to improve outcomes for acute type A aortic dissection with cerebral malperfusion.

OBJECTIVES: We aimed to identify predictors of postoperative permanent neurological deficits (PNDs) and evaluate the early management of cerebral perfusion in patients undergoing surgical repair of acute type A aortic dissection with cerebral malperfusion. METHODS: Between October 2009 and September 2018, a total of 197 patients with acute type A aortic dissection underwent aortic replacement. Of these, 42 (21.3%) patients had an imaging cerebral malperfusion (ICM). ICM was assessed preoperatively, which also revealed whether dissected supra-aortic branch vessels were occluded or narrowed by a thrombosed false lumen. After September 2017, early reperfusion and extra-anatomic revascularization were performed in cases with ICM. RESULTS: Hospital mortality rates for cases with ICM were 4.8% (2/42). Before September 2017, PND were observed in 6 patients (54.5%) with preoperative neurological symptoms (n = 11), and 7 patients (33.3%) without neurological symptoms (n = 21) in patients with ICM. Occlusion or severe stenosis of supra-aortic branch vessels (odds ratio, 7.66; P < 0.001), regardless of preoperative clinical neurological symptoms, was a risk factor for PND. After September 2017, 7 of 10 patients with ICM underwent early reperfusion and extra-anatomic revascularization. PND did not occur in any of these 7 patients. CONCLUSIONS: Occlusion or severe stenosis of supra-aortic branch vessels is a predictor of PND risk in patients undergoing surgery for acute type A aortic dissection. Early reperfusion and extra-anatomic revascularization may reduce the risk of neurological complications in patients with ICM, with or without neurological symptoms.

Parallel Placement of Excluder Legs for the Treatment of a Type IIIb Endoleak Using AFX2.

Endoleak is a major complication of endovascular aneurysm repair (EVAR). Type IIIb endoleaks, which are caused by endograft fabric disruption, are relatively rare. Although relining of the previously placed endograft with another main endograft is considered an ideal approach, it is sometimes difficult. The efficacy of parallel placement of Excluder legs has been reported in various settings. Here, we report the successful treatment of a type IIIb endoleak with parallel placement of Excluder legs during EVAR by using an AFX2 device.

Relevance of Aortic Dissection Chronicity to the Development of Stent Graft-induced New Entry.

BACKGROUND: The relevance of aortic dissection chronicity to the development of stent graft-induced new entry (SINE) is unknown. METHODS: This study enrolled 69 patients who underwent thoracic endovascular aortic repair (TEVAR) for chronic aortic dissection from January 2006 to December 2017 and were followed up for ≥6 months. Their medical records were reviewed retrospectively. Patients were stratified according to TEVAR timing into an early group (≤6 months from the onset of aortic dissection) and a late group (>6 months after the onset). The incidence of SINE as well as the interval between TEVAR and the development of SINE was compared between these groups. RESULTS: During the follow-up period, SINE occurred in 12% (3/26) and 35% (15/43) of patients in the early and late groups, respectively (P = .029). The interval between TEVAR and SINE development was significantly longer in the late group than the early group (median, 92 days vs 1144 days, respectively; P = .002). According to the multivariate analysis results, the late group (hazard ratio, 3.667; 95% confidence interval, 1.037-12.968; P = .044) and the distal oversizing ratio (hazard ratio, 1.492; 95% confidence interval, 1.071-2.080; P = .018) were the independent predictors for SINE development. CONCLUSIONS: TEVAR should be performed in the early period of the chronic phase to prevent SINE. Close and lifelong follow-up is mandatory for patients who undergo TEVAR >6 months after onset because SINE can develop several years after TEVAR in those patients.