Early Experience With Fenestration Modification of Castor Branched Stent-Graft for Aortic Arch Diseases.

PURPOSE: This study aimed to assess the safety and viability of combining branched stent graft with fenestrated thoracic endovascular aortic repair (TEVAR) in treating aortic arch lesions. MATERIALS AND METHODS: The cohort included patients presenting with aortic arch lesions who underwent treatment with a combination of branched stent graft and fenestrated TEVAR between July 2020 and November 2022. Technical success was defined as the precise deployment of the stent graft, maintenance of branch vessel patency, and the absence of type I endoleak. The secondary outcomes examined were complications and all-cause mortality. RESULTS: The study cohort comprised 21 patients (average age: 61.0±14.8 years) with aortic arch lesions from 3 tertiary care hospitals. The aortic arch lesions encompassed aortic dissection (N=8), aortic aneurysm (N=8), pseudoaneurysm (N=1), intramural hematoma (N=1), and penetrating aortic ulcer (N=3). The technical success rate achieved was 95.2% (20/21). Failure in one case was due to an intraoperative type I endoleak, which was rectified with an additional stent graft placement. The 30-day mortality rate was 4.8% (1/21). One patient suffered a stroke but responded well to medical intervention. The median hospital stay was 10.9±5.4 days. During the follow-up period, one death (4.8%) was associated with aortic complications. A type II endoleak was observed and managed with close monitoring. Two patients underwent re-interventions for retrograde type A dissection and stent migration, respectively. No occlusions were observed in the target branch arteries. CONCLUSIONS: The combination of branched stent graft with fenestrated TEVAR emerges as a viable strategy for addressing specific lesions in the aortic arch. CLINICAL IMPACT: This study demonstrates the feasibility of using branched stent grafts with fenestrated TEVAR for treating aortic arch lesions, achieving a technical success rate of 95.2%. Compared to traditional open surgery, this innovative, minimally invasive approach reduces perioperative mortality and complications, such as stroke and spinal cord ischemia. For clinicians, it offers a viable alternative for patients unfit for open repair, particularly in complex aortic arch cases. While the initial outcomes are promising, further research is needed to assess long-term durability and risks, including stent graft migration and late endoleak, ensuring the technique's safety and efficacy over time.

Selenium Deficiency Promotes Dilatation of the Aorta by Increasing Expression and Activity of Vascular Smooth Muscle Cell Derived Matrix Metalloproteinase-2.

OBJECTIVE: Selenium (Se) is a key part of the body's oxidation defence system. However, it is unclear whether Se affects the development of aortic aneurysm (AA). An animal experiment was conducted to clarify the role of Se in AA development. METHODS: C57BL/6N male mice were fed with a Se deficient (Se-D, < 0.05 mg/kg), Se adequate (Se-A, 0.2 mg/kg), or Se supplemented (Se-S, 1 mg/kg) diet for 8 weeks. Subsequently, an AA murine model (Se-D, n = 11; Se-A, n = 12; Se-S, n = 15) was established using angiotensin II (Ang II, 1 mg/kg/min) for four weeks plus ß-aminopropionitrile (BAPN, 1 mg/mL) for the first two weeks. Saline replaced Ang II, and BAPN was removed during the modelling process for sham mice (Se-A, n = 9). To determine whether Se deficiency promoted aortic dilation via matrix metalloproteinase-2 (MMP-2), the non-specific MMP inhibitor doxycycline (Dox, 100 mg/kg/day) was given to Se-D AA mice (n = 7) for two weeks. RESULTS: The maximum aortic diameter in Se-D AA model mice was significantly increased compared with Se-A AA model mice. MMP-2 expression and activity in the aortic media of Se-D AA model mice was significantly increased compared with Se-A AA model mice. A large number of vascular smooth muscle cells (VSMCs) were found aggregating in the media of the non-dilated aorta of Se-D AA model mice, which was completely inhibited by Dox. The percentage of VSMCs in aortic media of Se-D AA model mice was significantly higher than in Se-A AA model mice. The maximum aortic diameter and occurrence rate of AA in Se-D AA model mice with Dox were significantly reduced compared with Se-D AA model mice. CONCLUSION: Se deficiency promoted dilatation of the aorta in AA model mice by increasing expression and activity of VSMC derived MMP-2, causing abnormal aggregation and proliferation of VSMCs in aortic media.

Pristimerin protects against pathological cardiac hypertrophy through improvement of PPARα pathway.

Pristimerin (PM), serving as a biological component mainly obtained from Celastraceae and Hippocrateaceae families, has been extensively explored for its numerous pharmacological activities, especially anti-cancer activity. However, the function of PM on pathological cardiac hypertrophy is poorly understood. This work was intended to investigate the effects of PM on pressure-overload induced myocardial hypertrophy and its potential pathways. Mouse model of pathological cardiac hypertrophy was generated by transverse aortic constriction (TAC) or minipump administration of the ß-adrenergic agonist ISO for 4 weeks, and PM (0.5 mg/Kg/d, i.p.) was treated for 2 weeks. PPARα-/- mice received TAC surgery were used for mechanism exploration. Moreover, neonatal rat cardiomyocytes (NRCMs) were utilized to explore the effect of PM following Angiotensin II (Ang II, 1.0 µM) administration. We found that PM attenuated pressure-overload induced cardiac dysfunction, myocardial hypertrophy and fibrosis in mice. Likewise, PM incubation dramatically reversed Ang II-mediated cardiomyocytes hypertrophy in NRCMs. RNA-Sequence showed that PM selectively contributed to improvement of PPARα/PGC1 signaling, while silencing PPARα abrogated the beneficial effects of PM on Ang II-treated NRCMs. Importantly, PM ameliorated Ang II-induced mitochondrial dysfunction and decrease in metabolic genes, whereas knockdown of PPARα eliminated these alterations in NRCMs. Similarly, PM presented limited protective effects on pressure-overload induced systolic dysfunction and myocardial hypertrophy in PPARα deficient mice. Overall, this study revealed that PM exerted protective activity against pathological cardiac hypertrophy through improvement of PPARα/PGC1 pathway.

Serum Ionized Calcium as a Prognostic Biomarker in Type B Aortic Dissection After Endovascular Treatment.

OBJECTIVE: Lower serum ionized calcium (iCa2+) was reported to be associated with a higher risk of adverse events in patients with cardiovascular diseases. This study aimed to investigate the associations between preoperative serum iCa2+ and outcomes of type B aortic dissection (TBAD) patients receiving thoracic endovascular aortic repair (TEVAR). METHODS: Between January 2016 and December 2019, 491 TBAD patients received TEVAR in a single center. Patients with acute or subacute TBAD were included. Serum iCa2+ (pH 7.4) was obtained from the arterial blood gas analysis before TEVAR. The study population was grouped into the hi-Ca group (1.11 mmol/L ≤ iCa2+ < 1.35 mmol/L) and lo-Ca group (iCa2+ < 1.11 mmol/L). The primary outcomes were all-cause mortality. The secondary outcomes were any major adverse clinical events (MACEs), which included all-cause mortality and aortic-related severe complications. To eliminate bias, 1:1 propensity score matching (PSM) was conducted. RESULTS: Overall, 396 TBAD patients were included in this study. In the total population, there were 119 (30.1%) patients in the lo-Ca group. After PSM, 77 matched pairs were obtained for further analysis. In the matched population, the 30-day mortality and 30-day MACEs between the two groups presented significant differences (p=0.023 and 0.029, respectively). At 5 years, cumulative incidences of mortality (log-rank p<0.001) and MACEs (log-rank p=0.016) were significantly higher in the lo-Ca group than that of the hi-Ca group. Multivariate cox regression analysis indicated that lower preoperative iCa2+ (hazard ratio for per 0.1 mmol/L decrease, 2.191; 95% confidence interval, 1.487-3.228, p<0.001) was an independent risk factor for 5-year mortality after PSM. CONCLUSIONS: Lower preoperative serum iCa2+ might have an association with 5-year mortality in TBAD patients after TEVAR. Serum iCa2+ monitoring in this population may facilitate the identification of critical conditions. CLINICAL IMPACT: Our present study found that the cutoff value of preoperative serum iCa2+ 1.11 mmol/L, which is slightly lower than the lower limit of the normal range of 1.15-1.35 mmol/L, worked relatively well for discerning the high-risk and low-risk TBAD patients at 5 years. Serum iCa2+ monitoring in TBAD patients receiving TEVAR may facilitate the identification of critical conditions.

Alpha-ketoglutarate ameliorates abdominal aortic aneurysm via inhibiting PXDN/HOCL/ERK signaling pathways.

Abdominal aortic aneurysm (AAA) represents the serious vascular degenerative disorder, which causes high incidence and mortality. Alpha-ketoglutarate (AKG), a crucial metabolite in the tricarboxylic acid (TCA) cycle, has been reported to exert significant actions on the oxidative stress and inflammation. However, its role in AAA still remains elusive. Herein, we examined the effects of AKG on the formation of AAA. The study established an elastase-induced mouse abdominal aortic aneurysms model as well as a TNF-α-mediated vascular smooth muscle cells (VSMCs) model, respectively. We displayed that AKG pre-treatment remarkably prevented aneurysmal dilation assessed by diameter and volume and reduced aortic rupture. In addition, it was also observed that AKG treatment suppressed the development of AAA by attenuating the macrophage infiltration, elastin degradation and collagen fibers remodeling. In vitro, AKG potently decreased TNF-α-induced inflammatory cytokines overproduction, more apoptotic cells and excessive superoxide. Mechanistically, we discovered that upregulation of vpo1 in AAA was significantly suppressed by AKG treatment. By exploring the RNA-seq data, we found that AKG ameliorates AAA mostly though inhibiting oxidative stress and the inflammatory response. PXDN overexpression neutralized the inhibitory effects of AKG on ROS generation and inflammatory reaction in MOVAS. Furthermore, AKG treatment suppressed the expression of p-ERK1/2, 3-Cl Tyr in vivo and in vitro. ERK activator disrupted the protective of AKG on TNF-α-induced VSMCs phenotypic switch. Conclusively, AKG can serve as a beneficial therapy for AAA through regulating PXDN/HOCL/ERK signaling pathways.

Long-Term Outcomes of Endovascular Treatment for Type B Aortic Dissection with Simple Renal Cysts: A Multicenter Retrospective Study.

Background: Few studies have investigated the characteristics and long-term outcomes of type B aortic dissection (BAD) patients with simple renal cysts (SRC) after thoracic endovascular aortic repair (TEVAR). Methods: A multi-center retrospective cohort study was performed, including 718 BAD patients undergoing TEVAR from 2003 to 2016. The prevalence of SRC was 34.5% (n = 248). After propensity score matching, 214 matched pairs were selected for further analysis. Primary outcomes were long-term aortic-related adverse events (ARAEs). The effects of SRC in each subgroup of interest and their interactions were analyzed. Results: BAD patients with SRC were older and had a greater prevalence of comorbidities, including hypertension, coronary artery disease and chronic occlusive pulmonary disease. In addition, the SRC group presented a greater proportion of pleural effusion and aortic calcification. Compared with the non-SRC group, a significantly higher maximal diameter of ascending aorta was observed in the SRC group. Apart from the timing of the operation, no differences were found in the medication regime or intra-operative parameters. In the matched population, patients with SRC were at a higher risk of ARAEs in the long term. The multivariable Cox model indicated that SRC was an independent predictor of long-term ARAEs (hazard ratio: 1.84, 95% confidence interval: 1.13-3.00). The interaction between SRC and hypertension on rupture after TEVAR was statistically significant (p = 0.023). Conclusions: Compared with the non-SRC group, BAD patients with SRC experienced a higher risk of long-term ARAEs after TEVAR. Among the SRC subgroup, hypertensive patients had the highest risk of rupture after TEVAR.

Outcomes of Total Endovascular Aortic Arch Repair with Surgeon-Modified Fenestrated Stent-Grafts on Zone 0 Landing for Aortic Arch Pathologies.

OBJECTIVES: This study evaluated the feasibility and safety of total endovascular aortic arch repair with surgeon-modified fenestrated stent-graft on zone 0 landing for aortic arch pathologies. METHODS: Between June 2016 and October 2019, 37 consecutive patients underwent total endovascular arch repair with surgeon-modified fenestrated stent-grafts on zone 0 landing. Outcomes included technical success, perioperative and follow-up morbidity and mortality, and branch artery patency. RESULTS: During the study period, 37 patients were treated with total endovascular aortic arch repair with surgeon-modified fenestrated stent-graft. Twenty-one (56.8%) patients were diagnosed with aortic dissections, 15 (40.5%) patients with aneurysms, and 1 (2.7%) patient required reintervention due to endoleak and sac expansion from previous thoracic endovascular aortic repair for thoracoabdominal aneurysm. The proximal landing zone for all patients were in zone 0, and all branch arteries of aortic arch were reconstructed. Technical success was achieved in 34 cases (91.9%). Three (8.1%) patients had fenestrations misaligned with target arteries, and the chimney technique was applied as a complementary measure. Thirty-day mortality rate was 5.4% (n=2). Thirty-day stroke rate was 5.4% (n=2). Thirty-day reintervention rate was 2.7% (n=1). At a median follow-up of 20 months (range, 3-49 months), 5 (13.5%) patients died, including 2 aortic-related deaths, 1 nonaortic-related death, and 2 deaths of unknown reason. One (2.7%) patient had stroke. Four patients (10.8%) had reintervention during the follow-up, including 2 cases of left subclavian artery occlusion and 2 cases of type II endoleak. The estimated survival (±SE) at 2 years was 72.4%±9.7% (95% CI 53.4%-91.4%). The estimated freedom from reintervention (±SE) at 2 years was 87.4%±5.9% (95% CI 75.84%-98.96%). CONCLUSIONS: Total endovascular aortic arch repair with surgeon-modified fenestrated stent-grafts on zone 0 landing is an alternate option for the treatment of aortic arch pathologies in experienced centers.

Outcomes of Zone 1 Thoracic Endovascular Aortic Repair With Fenestrated Surgeon-Modified Stent-Graft for Aortic Arch Pathologies.

OBJECTIVES: This study evaluated the feasibility and safety of zone 1 thoracic endovascular aortic repair (TEVAR) with fenestrated surgeon-modified stent-graft (SMSG) for aortic arch pathologies. METHODS: Between March 2016 and November 2020, 34 consecutive patients underwent zone 1 TEVAR with fenestrated SMSG for aortic arch pathologies. Outcomes included technical success, perioperative, and follow-up morbidity and mortality. RESULTS: During the study period, 34 patients were treated with zone 1 TEVAR with fenestrated SMSG. Twenty-four (70.6%) patients presented with type B aortic dissections, 9 (26.5%) patients presented with aneurysms (7 located on the lesser curvature side of aortic arch), 1 (2.9%) patient presented with type Ia endoleak after previous TEVAR owing to traumatic aortic dissection. The proximal landing zone for all patients were in zone 1, and all supra-aortic trunks were reconstructed, except for one left subclavian artery. Technical success was achieved in all cases. The 30-day estimated survival (±SE) was 90.9% ± 5.0% [95% confidence interval (CI): 77.0%-97.0%]. The 30-day estimated freedom from reintervention (±SE) was 87.9% ± 5.7% (95% CI: 73.4%-95.3%). At a median follow-up of 48 months (range, 12-68 months), 2 patients died, including 1 aortic-related death and 1 non-aortic-related death. One patient had reintervention 13 months after the operation owing to type Ia endoleak. All supra-aortic trunks were patent. The estimated survival (±SE) during follow-up was 85.1% ± 6.2% (95% CI: 69.9%-93.6%). One (2.7%) patient had stroke. The estimated freedom from reintervention (±SE) during follow-up was 84.2% ± 6.5% (95% CI: 69.9%-93.5%). CONCLUSIONS: Zone 1 TEVAR with fenestrated SMSG is an alternate option for treatment of aortic arch pathologies in experienced centers.

False Lumen Stent-Grafts for Repair of Postdissection Aortic Aneurysms.

PURPOSE: To evaluate the safety and efficacy of false lumen (FL) stent-grafts in the treatment of postdissection aortic aneurysms. MATERIALS AND METHODS: Eleven patients who underwent endovascular repair using FL stent-grafts from January 2016 to June 2019 were included. Among them, 2 patients had a prior history of type A aortic dissection, whereas 9 had undergone a prior endovascular repair for type B aortic dissection. Computed tomography angiography was performed to evaluate the reintervention and technical success rate, aortic remodeling, and other related aortic complications. RESULTS: The mean age of patients was 55.6 ± 10.4 years. Technical success was achieved in all patients, and neither early mortality nor paralysis occurred. In total, 8 visceral branch arteries originating from the FL were reconstructed. The true lumen areas at the celiac axis, superior mesenteric artery, renal artery, and abdominal aortic bifurcation were significantly increased from 230.1 mm2 to 312.3 mm2, 212.1 mm2 to 277.5 mm2, 209.1 mm2 to 291.6 mm2, and 214.4 mm2 to 300.6 mm2, respectively (P < .05). The total diameter of the aorta at the 4 designated levels was stable or had shrunk in all patients. At a mean follow-up of 18.9 ± 7.6 months, 1 patient received re-intervention owing to iliac stent-graft occlusion. No aortic-related mortality occurred. CONCLUSIONS: FL stent-grafts can safely and effectively treat patients with postdissection aortic aneurysms. This strategy can be used to promote thrombosis of the FL and aortic remodeling. A larger sample and an extended follow-up period are needed to produce more conclusive results.

Elevated preoperative neutrophil-to-lymphocyte ratio predicts early adverse outcomes in uncomplicated type B aortic dissection undergoing TEVAR.

BACKGROUND: Thoracic aortic endovascular repair (TEVAR) of uncomplicated type B aortic dissection (uTBAD) has favorable long-term outcomes but higher early adverse events compared with the optimal medical treatment. Recently, clinical evidence concerning vascular surgery indicates that elevated preoperative systemic inflammatory response predicts adverse clinical events. The aim of our study was to evaluate the relationship between preoperative neutrophil-to-lymphocyte ratio (NLR) and early outcomes of uTBAD patients undergoing TEVAR. RESULTS: 216 patients diagnosed with uTBAD were included in this retrospective study between January 2015 and December 2018. The median (IQR) follow-up period was 21 (15-33) months. An early adverse event was defined as occurring within 2 years after the procedure. Median patient age was 60 (IQR, 48-68) years and 78.7 % were male. Early adverse events occurred in 24 patients (11.1 %). In the multivariable analysis, preoperative NLR (HR per SD, 1.98; 95 % CI, 1.14-3.44; P = 0.015) was associated with 2-year adverse events. CONCLUSIONS: NLR is an independent predictive factor of early adverse events in uTBAD patients undergoing TEVAR.