Pentamethylquercetin attenuates angiotensin II-induced abdominal aortic aneurysm formation by blocking nuclear translocation of C/EBPß at Lys253.

BACKGROUND: Pentamethylquercetin (PMQ) is a natural polymethyl flavonoid that possesses anti-apoptotic and other biological properties. Abdominal aortic aneurysm (AAA), a fatal vascular disease with a high risk of rupture, is associated with phenotypic switching and apoptosis of medial vascular smooth muscle cells (VSMCs). This study aimed to investigate the protective effects of PMQ on the development of AAA and the underlying mechanism. METHODS: ApoE-/- mice were continuously infused with angiotensin II (Ang II) for 4 weeks to develop the AAA model. Intragastric administration of PMQ was initiated 5 days before Ang II infusion and continued for 4 weeks. In vitro, VSMCs were cultured and pretreated with PMQ, stimulated with Ang II. Real-time PCR, western blotting, and immunofluorescence staining were used to examine the roles and mechanisms of PMQ on the phenotypic switching and apoptosis of VSMCs. RESULTS: PMQ dose-dependently reduced the incidence of Ang II-induced AAA, aneurysm diameter enlargement, elastin degradation, VSMCs phenotypic switching and apoptosis. Furthermore, PMQ also inhibited phenotypic switching and apoptosis in Ang II-stimulated VSMCs. PMQ exerted protective effects by regulating the C/EBPß/PTEN/AKT/GSK-3ß axis. AAV-mediated overexpression of PTEN reduced the therapeutic effects of PMQ in the AAA model mice, suggesting that the effects of PMQ on Ang II-mediated AAA formation were related to the PTEN/AKT/GSK-3ß axis. PMQ inhibited VSMCs phenotypic switching and apoptosis by bounding to C/EBPß at Lys253 with hydrogen bond to regulate C/EBPß nuclear translocation and PTEN/AKT/GSK-3ß axis, thereby inhibiting Ang II-induced AAA formation. CONCLUSIONS: Pentamethylquercetin inhibits angiotensin II-induced abdominal aortic aneurysm formation by bounding to C/EBPß at Lys253. Therefore, PMQ prevents the formation of AAA and reduces the incidence of AAA.

Successful chimney endovascular aortic repair with reconstruction of three visceral branches for huge saccular juxtarenal abdominal aortic aneurysm after trans-thoracoabdominal esophagectomy.

BACKGROUND: Conventional graft replacement for a juxtarenal abdominal aortic aneurysm (JRAAA) remains challenging for high-risk patients since it often requires the reconstruction of some visceral arteries. CASE PRESENTATION: A 76-year-old woman was diagnosed with an 87 × 48 mm saccular JRAAA. Open graft replacement was contraindicated because of frailty and a past history of trans-thoracoabdominal esophagectomy. Chimney endovascular aortic repair (ChEVAR) with three chimney endografts was successfully performed without any endoleaks, and each visceral circulation was kept intact. The patient was discharged uneventfully on postoperative day 8. Significant shrinkage of the aneurysmal sac and preservation of flow through each chimney graft were observed on computed tomography 6 months postoperatively, with no significant increase in serum creatinine levels on laboratory testing. CONCLUSIONS: ChEVAR can be a useful surgical option instead of conventional operations, especially for high-risk cases.

Comment on Rehman et al. "Short-Term Outcomes of Elective Abdominal Aortic Aneurysm Repair".

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Protocol for an independent patient data meta-analysis of prophylactic mesh placement for incisional hernia prevention after abdominal aortic aneurysm surgery: a collaborative European Hernia Society project (I-PREVENT-AAA).

INTRODUCTION: Incisional hernia (IH) is a prevalent and potentially dangerous complication of abdominal surgery, especially in high-risk groups. Mesh reinforcement of the abdominal wall has been studied as a potential intervention to prevent IHs. Randomised controlled trials (RCTs) have demonstrated that prophylactic mesh reinforcement after abdominal surgery, in general, is effective and safe. In patients with abdominal aortic aneurysm (AAA), prophylactic mesh reinforcement after open repair has not yet been recommended in official guidelines, because of relatively small sample sizes in individual trials. Furthermore, the identification of subgroups that benefit most from prophylactic mesh placement requires larger patient numbers. Our primary aim is to evaluate the efficacy and effectiveness of the use of a prophylactic mesh after open AAA surgery to prevent IH by performing an individual patient data meta-analysis (IPDMA). Secondary aims include the evaluation of postoperative complications, pain and quality of life, and the identification of potential subgroups that benefit most from prophylactic mesh reinforcement. METHODS AND ANALYSIS: We will conduct a systematic review to identify RCTs that study prophylactic mesh placement after open AAA surgery. Cochrane Central Register of Controlled Trials, MEDLINE Ovid, Embase, Web of Science Core Collection and Google Scholar will be searched from the date of inception onwards. RCTs must directly compare primary sutured closure with mesh closure in adult patients who undergo open AAA surgery. Lead authors of eligible studies will be asked to share individual participant data (IPD). The risk of bias (ROB) for each included study will be assessed using the Cochrane ROB tool. An IPDMA will be performed to evaluate the efficacy, with the IH rate as the primary outcome. Any signs of heterogeneity will be evaluated by Forest plots. Time-to-event analyses are performed using Cox regression analysis to evaluate risk factors. ETHICS AND DISSEMINATION: No new data will be collected in this study. We will adhere to institutional, national and international regulations regarding the secure and confidential sharing of IPD, addressing ethics as indicated. We will disseminate findings via international conferences, open-source publications in peer-reviewed journals and summaries posted online. PROSPERO REGISTRATION NUMBER: CRD42022347881.

Impact of iliac access in elective and non-elective endovascular repair of abdominal aortic aneurysm.

Endovascular aortic repair (EVAR) is nowadays the establishment treatment for patients with abdominal aortic aneurysm (AAA) both in elective and urgent setting. Despite the large applicability and satisfactory results, the presence of hostile iliac anatomy affects both technical and clinical success. This narrative review aimed to report the impact of iliac access and related adjunctive procedures in patients undergoing EVAR in elective and non-elective setting. Hostile iliac access can be defined in presence of narrowed, tortuous, calcified, or occluded iliac arteries. These iliac characteristics can be graded by the anatomic severity grade score to quantitatively assess anatomic complexity before undergoing treatment. Literature shows that iliac hostility has an impact on device navigability, insertion and perioperative and postoperative results. Overall, it has been correlated to higher rate of access issues, representing up to 30% of the first published EVAR experience. Recent innovations with low-profile endografts have reduced large-bore sheaths related issues. However, iliac-related complications still represent an issue, and several adjunctive endovascular and surgical strategies are nowadays available to overcome these complications during EVAR. In urgent settings iliac hostility can significantly impact on particular time sensitive procedures. Moreover, in case of severe hostility patients might be written off for EVAR repair might be inapplicable, exposing to higher mortality/morbidity risk in this urgent/emergent setting. In conclusion, an accurate anatomical evaluation of iliac arteries during preoperative planning, materials availability, and skilled preparation to face iliac-related issues are crucial to address these challenges.

Physician-modified versus chimney endografting for pararenal aortic aneurysms: a systematic review and meta-analysis.

INTRODUCTION: We performed a systematic review and meta-analysis to assess the existing published evidence regarding the safety and efficacy of the endovascular aortic repair with chimney technique (ch-EVAR) and physician-modified stent-grafts (PMSGs) for the treatment of pararenal aortic aneurysm repair. EVIDENCE ACQUISITION: A systematic search of all relevant studies reported until October 2023 according to the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines was performed. The pooled 30-day mortality, peri- and postoperative complication rates were estimated using fixed or random effect methods. EVIDENCE SYNTHESIS: A total of 679 study titles were identified by the initial search strategy, of which 16 were considered eligible for inclusion in the meta-analysis. A total of 1094 patients (ch-EVAR N.=861 and PMSG N.=233) (90% male) were identified. The pooled 30-day mortality rate was 3.4% for ch-EVAR and 2.6% for PMSG. The major adverse events (MAE) in the early period was 14.7% for ch-EVAR and 18.5% PMSG, respectively. Higher occlusion rate was observed of the chimney stents grafts (8.2%) than the bridging stents (1.4%) during the follow-up period. CONCLUSIONS: Ch-EVAR and physician-modified technology are safe with low 30-day mortality in elective settings for pararenal aortic aneurysms repair. No significant differences were seen between the two surgical methods regarding the early major adverse events rate. However, higher occlusion rate for the chimneys can be expected over time.

Protagoras 3.0: feasibility of current fenestrated endografts and chimney technique for complex abdominal aortic aneurysms.

BACKGROUND: The aim of this study was to evaluate the anatomical feasibility of current available fenestrated endografts (FEVAR) and on-label chimney technique (EnChEVAR) in patients with complex abdominal aortic aneurysms (C-AAA). METHODS: Feasibility of EnChEVAR (Endurant II/IIS CE-marked [Medtronic]) and 4 types of FEVAR (Zenith Fenestrated CE-marked, Zenith Fenestrated Low-Profile [LP] custom-made device [CMD] [Cook Medical], Fenestrated Anaconda LoPro90 CMD, Fenestrated Treo CMD [Terumo Aortic]) was assessed according to the manufacturer's instructions for use. Computed tomography angiograms of patients with C-AAA previously included in the Protagoras 2.0 study were retrospectively reviewed. The aortic coverage was ideally planned to involve a maximum of two chimney grafts or fenestrations. RESULTS: Iliac access and aortic neck of 73 C-AAAs were analyzed. The overall feasibility was significantly different between EnChEVAR (33%) and FEVAR (Zenith Fenestrated 15%, Zenith Fenestrated LP 15%, Fenestrated Anaconda LoPro90 45%, Fenestrated Treo 48%). The iliac access feasibility was significantly lower for Zenith Fenestrated with standard profile compared to all other grafts. The aortic neck feasibility was significantly higher for EnChEVAR and both Terumo Aortic fenestrated stent grafts, compared to both Cook Medical grafts. The treatment using any of the three current available fenestrated grafts with lower profile (Zenith Fenestrated LP, Fenestrated Anaconda LoPro90, Fenestrated Treo) would have been feasible in 71% of the cases. CONCLUSIONS: Most of the patients treated by ChEVAR would have not been treated by first generation fenestrated stent graft. The current available fenestrated endografts, with lower profile and suitable also for angulated necks, increase the anatomical feasibility.

Early multicentric outcomes of the on-label and CE-marked combination of the Endurant with the Radiant chimney graft for the chimney endovascular aortic repair (EnChEVAR): The LaMuR Registry.

BACKGROUND: The aim of this study was to evaluate the early results of the CE-marked standardized device combination consisting of Endurant and the Radiant chimney graft (En-ChEVAR) for the treatment of juxtarenal aortic aneurysms. METHODS: We analyzed multicentric non-industry sponsored case series evaluating the EnChEVAR technique for patients treated between December 2022 and February 2024. Clinical, perioperative procedure-related and radiological data were collected. The primary outcome measure was the freedom of a type Ia gutter-related endoleak at postoperative computed tomography angiography (CTA). Secondary outcome measures included early type Ia endoleak-related reinterventions, target vessel complications including dissection or loss of target vessel, major adverse events, and mortality. Continuous variables were presented as median (interquartile range [IQR]) and categorical variables as count and percentage. RESULTS: Ten patients were included in the present study. Eight (80%) were males, in nine cases a single chimney was implanted, and the other one was a double chimney graft placement. The treated aneurysms had an infrarenal neck length of 3.4 (1.2) mm. The rate of main body oversizing was 30%. The new neck length after chimney graft placement was 18 (3) mm. The median procedural time was 130 (17) mm, contrast medium use was 109 (26) mL, radiation time was 45 (12) min. The technical success was 100%. No type Ia endoleak was detected at the postoperative CTA. There were no target vessel issues. No major adverse events or death were observed. CONCLUSIONS: First reported cohort of patients treated with EnChEVAR demonstrated reproducible clinical and procedural outcomes within the 3 vascular centers with total exclusion of the aneurysms, patent renal arteries, and no evidence of gutter-related type IA endoleak. Further evidence with larger sample size of treated patients and longer follow-up are needed.

Smooth-Muscle-Cell-Specific Deletion of CD38 Protects Mice from AngII-Induced Abdominal Aortic Aneurysm through Inhibiting Vascular Remodeling.

Abdominal aortic aneurysm (AAA) is a serious vascular disease which is associated with vascular remodeling. CD38 is a main NAD+-consuming enzyme in mammals, and our previous results showed that CD38 plays the important roles in many cardiovascular diseases. However, the role of CD38 in AAA has not been explored. Here, we report that smooth-muscle-cell-specific deletion of CD38 (CD38SKO) significantly reduced the morbidity of AngII-induced AAA in CD38SKOApoe-/- mice, which was accompanied with a increases in the aortic diameter, medial thickness, collagen deposition, and elastin degradation of aortas. In addition, CD38SKO significantly suppressed the AngII-induced decreases in α-SMA, SM22α, and MYH11 expression; the increase in Vimentin expression in VSMCs; and the increase in VCAM-1 expression in smooth muscle cells and macrophage infiltration. Furthermore, we demonstrated that the role of CD38SKO in attenuating AAA was associated with the activation of sirtuin signaling pathways. Therefore, we concluded that CD38 plays a pivotal role in AngII-induced AAA through promoting vascular remodeling, suggesting that CD38 may serve as a potential therapeutic target for the prevention of AAA.

Endovascular repair of an abdominal aortic aneurysm with external iliac artery occlusion using VBX as the contralateral leg via axillary delivery: A case report.

RATIONALE: A hostile iliac access route is an important consideration when enforcing endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms (AAA). Herein, we report a case of AAA with unilateral external iliac artery occlusion, for which bifurcated EVAR was successfully performed using a single femoral and brachial artery access. PATIENT CONCERNS: A 76-year-old man who had undergone surgery for lung cancer 4.5 years prior was diagnosed AAA by computed tomography (CT). DIAGNOSIS: Two and a half years before presentation, CT revealed an infrarenal 48 mm AAA, which had enlarged to 57 mm by 2 months preoperatively. CT identified occlusion from the right external iliac artery to the right common femoral artery, with no observed ischemic symptoms in his right leg. The right external iliac artery, occluded and atrophied, had a 1 to 2 mm diameter. INTERVENTION: Surgery was commenced with the selection of a Zenith endovascular graft (Cook Medical) with an extended body length. Two Gore Viabahn VBX balloon expandable endoprosthesis (VBX; W.L. Gore & Associate) were delivered from the right axilla as the contralateral leg. OUTCOMES: CT scan on the 2nd day after surgery revealed no endoleaks. LESSONS: While the long-term results remain uncertain, this method may serve as an option for EVAR in patients with unilateral external iliac artery occlusion.

Image-based assessment of aortoiliac aneurysm anatomical characteristics in patients from the global iliac branch study.

OBJECTIVE: Endovascular repair is the preferred treatment for aortoiliac aneurysm, with preservation of at least one internal iliac artery recommended. This study aimed to assess pre-endovascular repair anatomical characteristics of aortoiliac aneurysm in patients from the Global Iliac Branch Study (GIBS, NCT05607277) to enhance selection criteria for iliac branch devices (IBD) and improve long-term outcomes. METHODS: Pre-treatment CT scans of 297 GIBS patients undergoing endovascular aneurysm repair were analyzed. Measurements included total iliac artery length, common iliac artery length, tortuosity index, common iliac artery splay angle, internal iliac artery stenosis, calcification score, and diameters in the device's landing zone. Statistical tests assessed differences in anatomical measurements and IBD-mediated internal iliac artery preservation. RESULTS: Left total iliac artery length was shorter than right (6.7 mm, P = .0019); right common iliac artery less tortuous (P = .0145). Males exhibited greater tortuosity in the left total iliac artery (P = .0475) and larger diameter in left internal iliac artery's landing zone (P = .0453). Preservation was more common on right (158 unilateral, 34 bilateral) than left (105 unilateral, 34 bilateral). There were 192 right-sided and 139 left-sided IBDs, with 318 IBDs in males and 13 in females. CONCLUSION: This study provides comprehensive pre-treatment iliac anatomy analysis in patients undergoing endovascular repair with IBDs, highlighting differences between sides and sexes. These findings could refine patient selection for IBD placement, potentially enhancing outcomes in aortoiliac aneurysm treatment. However, the limited number of females in the study underscores the need for further research to generalize findings across genders.

Postoperative serum mir-28-5p level has predictive value for the prognosis after endovascular abdominal aortic aneurysm repair.

BACKGROUND: We explored the clinical significance of miR-28-5p pre- and post-endovascular abdominal aortic aneurysm repair (EVAR) in abdominal aortic aneurysm (AAA) patients. METHODS: Subjects included AAA patients receiving EVAR and non-AAA people without statistical differences from AAA patient in comorbidities/Framingham risk score. Fasting elbow venous blood (4 mL) was collected in the morning of the day of EVAR surgery and in the morning of 3 months post-EVAR. Pre-/post-EVAR serum miR-28-5p expression, AAA maximum diameter alterations, CD3+/CD4+/CD8+/TC/TG pre-/post-EVAR, and the correlations between miR-28-5p and AAA maximum diameter were investigated. Prediction of miR-28-5p on post-EVAR mortality, prognosis, and independent factors of post-EVAR death were analyzed using receiver operating characteristic curve (ROC)/Kaplan-Meier curve/univariable and multivariable Cox regression. According to the cut-off value of ROC curve for postoperative miR-28-5p was the cut-off value, and the patients were classified into the miR-28-5p high- and low-expression groups. The survival or death of both groups were compared after 48-month follow-up. RESULTS: Serum miR-28-5p levels in AAA patients dropped post-EVAR. AAA patients showed notable differences in CD3+/CD4+/CD8+/TC/TG levels pre-/post-EVAR. The miR-28-5p low-expression group exhibited higher CD3+/CD4+ and lower CD8+/TC/TG levels. We observed a positive correlation between post-EVAR miR-28-5p and AAA maximum diameter and between the pre-/post-EVAR miR-28-5p fold change and the AAA maximum diameter change. Postoperative miR-28-5p demonstrated good predictive value for postoperative death. Hypertension, Framingham risk score, TC, TG, and miR-28-5p were independent influencing factors of post-EVAR death. CONCLUSION: EVAR decreased serum miR-28-5p expression in AAA patients. Post-operative miR-28-5p level and pre-/post-operative fold change level are positively-correlated with AAA diameter.

Surgeon-modified fenestrated endovascular grafts and thoracoscope-assisted fixation for treatment of thoraco-abdominal aortic aneurysms.

BACKGROUND: Total endovascular technique with fenestrated endovascular graft might be hampered for the late dilatation of proximal landing zone, which may cause endografts migration. We describe a successful urgent hybrid procedure for extent III thoracoabdominal aortic aneurysm with aortic intramural hematoma. CASE PRESENTATION: A 55-year-old female with thoracoabdominal aortic aneurysm was considered at high surgical risk and unfit for open repair due to multiple comorbidities. Therefore, a hybrid procedure of surgeon-modified fenestrated endovascular graft combined with thoracoscope-assisted Transaortic epicardial fixation of endograft was finally chosen and performed in the endovascular operating room. A 3-port technique was performed through a left video-assisted thoracoscopic approach. After the first tampering stent-graft was deployed, a double-needle suture was penetrated both the aortic wall and stent-graft to fixate it in the proximal descending aorta. Then the second endograft, which had been fenestrated on table, was introduced and oriented extracorporeally by rotating superior mesenteric artery and left renal artery fenestration radiopaque markers and deployed with perfect apposition between the fenestrations and target visceral artery. Each vessel was sequentially stented using Viabahn self-expandable stent to finish target vessel stenting. An Ankura cuff stent was deployed in the distal abdominal aortic artery. CONCLUSION: Surgeon-modified fenestrated endovascular graft combined with thoracoscope-assisted fixation may be an innovative and viable alternative for selected high-risk patients with extent III thoracoabdominal aortic aneurysm. A longer follow-up is needed to ascertain the success of this approach.

Resolvin D2 prevents vascular remodeling, hypercontractility and endothelial dysfunction in obese hypertensive mice through modulation of vascular and proinflammatory factors.

During resolution of inflammation, specialized proresolving mediators (SPMs), including resolvins, are produced to restore tissue homeostasis. We hypothesized that there might be a dysregulation of SPMs pathways in pathological vascular remodeling and that resolvin D2 (RvD2) might prevent vascular remodeling and contractile and endothelial dysfunction in a model of obesity and hypertension. In aortic samples of patients with or without abdominal aortic aneurysms (AAA), we evaluated gene expression of enzymes involved in SPMs synthesis (ALOXs), SPMs receptors and pro-inflammatory genes. In an experimental model of aortic dilation induced by high fat diet (HFD, 60%, eighteen weeks) and angiotensin II (AngII) infusion (four weeks), we studied the effect of RvD2 administration in aorta and small mesenteric arteries structure and function and markers of inflammation. In human macrophages we evaluated the effects of AngII and RvD2 in macrophages function and SPMs profile. In patients, we found positive correlations between AAA and obesity, and between AAA and expression of ALOX15, RvD2 receptor GPR18, and pro-inflammatory genes. There was an inverse correlation between the expression of aortic ALOX15 and AAA growth rate. In the mice model, RvD2 partially prevented the HFD plus AngII-induced obesity and adipose tissue inflammation, hypertension, aortic and mesenteric arteries remodeling, hypercontratility and endothelial dysfunction, and the expression of vascular proinflammatory markers and cell apoptosis. In human macrophages, RvD2 prevented AngII-induced impaired efferocytosis and switched SPMs profile. RvD2 might represent a novel protective strategy in preventing vascular damage associated to hypertension and obesity likely through effects in vascular and immune cells.

Computed tomography-based automated measurement of abdominal aortic aneurysm using semantic segmentation with active learning.

Accurate measurement of abdominal aortic aneurysm is essential for selecting suitable stent-grafts to avoid complications of endovascular aneurysm repair. However, the conventional image-based measurements are inaccurate and time-consuming. We introduce the automated workflow including semantic segmentation with active learning (AL) and measurement using an application programming interface of computer-aided design. 300 patients underwent CT scans, and semantic segmentation for aorta, thrombus, calcification, and vessels was performed in 60-300 cases with AL across five stages using UNETR, SwinUNETR, and nnU-Net consisted of 2D, 3D U-Net, 2D-3D U-Net ensemble, and cascaded 3D U-Net. 7 clinical landmarks were automatically measured for 96 patients. In AL stage 5, 3D U-Net achieved the highest dice similarity coefficient (DSC) with statistically significant differences (p < 0.01) except from the 2D-3D U-Net ensemble and cascade 3D U-Net. SwinUNETR excelled in 95% Hausdorff distance (HD95) with significant differences (p < 0.01) except from UNETR and 3D U-Net. DSC of aorta and calcification were saturated at stage 1 and 4, whereas thrombus and vessels were continuously improved at stage 5. The segmentation time between the manual and AL-corrected segmentation using the best model (3D U-Net) was reduced to 9.51 ± 1.02, 2.09 ± 1.06, 1.07 ± 1.10, and 1.07 ± 0.97 min for the aorta, thrombus, calcification, and vessels, respectively (p < 0.001). All measurement and tortuosity ratio measured - 1.71 ± 6.53 mm and - 0.15 ± 0.25. We developed an automated workflow with semantic segmentation and measurement, demonstrating its efficiency compared to conventional methods.

Neutrophil Extracellular Traps in Cardiovascular and Aortic Disease: A Narrative Review on Molecular Mechanisms and Therapeutic Targeting.

Neutrophil extracellular traps (NETs), composed of DNA, histones, and antimicrobial proteins, are released by neutrophils in response to pathogens but are also recognized for their involvement in a range of pathological processes, including autoimmune diseases, cancer, and cardiovascular diseases. This review explores the intricate roles of NETs in different cardiovascular conditions such as thrombosis, atherosclerosis, myocardial infarction, COVID-19, and particularly in the pathogenesis of abdominal aortic aneurysms. We elucidate the mechanisms underlying NET formation and function, provide a foundational understanding of their biological significance, and highlight the contribution of NETs to inflammation, thrombosis, and tissue remodeling in vascular disease. Therapeutic strategies for preventing NET release are compared with approaches targeting components of formed NETs in cardiovascular disease. Current limitations and potential avenues for clinical translation of anti-NET treatments are discussed.

Latest evidence on chimney endovascular repair of abdominal aortic aneurysms and the renal artery angulation pitfall.

This article summarizes the key findings in literature up to date on the endovascular treatment of complex abdominal aortic aneurysms (AAAs) employing the chimney technique. Additionally, an unexplored pitfall is described regarding the target vessel angulation. Although balloon-expandable covered stents present more favorable configuration in downward-oriented target vessels, transverse and upward-oriented target vessels may benefit from other endovascular techniques imploring careful case planning and further investigation on the topic.