Weiguo Fu

Mechanisms of symptomatic spinal cord ischemia after TEVAR: insights from the European Registry of Endovascular Aortic Repair Complications (EuREC).

Purpose To test the hypothesis that simultaneous closure of at least 2 independent vascular territories supplying the spinal cord and/or prolonged hypotension may be associated with symptomatic spinal cord ischemia (SCI) after thoracic endovascular aortic repair (TEVAR). Methods A pattern matching algorithm was used to develop a risk model for symptomatic SCI using a prospective 63-patient single-center cohort to test the positive predictive value (PPV) of prolonged intraoperative hypotension and/or simultaneous closure of at least 2 of 4 the vascular territories supplying the spinal cord (left subclavian, intercostal, lumbar, and hypogastric arteries). This risk model was then applied to data extracted from the multicenter European Registry on Endovascular Aortic Repair Complications (EuREC). Between 2002 and 2010, the 19 centers participating in EuREC reported 38 (1.7%) cases of symptomatic spinal cord ischemia among the 2235 patients in the database. Results In the single-center cohort, direct correlations were seen between the occurrence of symptomatic SCI and both prolonged intraoperative hypotension (PPV 1.00, 95% CI 0.22 to 1.00, p=0.04) and simultaneous closure of at least 2 independent spinal cord vascular territories (PPV 0.67, 95% CI 0.24 to 0.91, p=0.005). Previous closure of a single vascular territory was not associated with an increased risk of symptomatic spinal cord ischemia (PPV 0.07, 95% CI 0.01 to 0.16, p=0.56). The combination of prolonged hypotension and simultaneous closure of at least 2 territories exhibited the strongest association (PPV 0.75, 95% CI 0.38 to 0.75, p<0.0001). Applying the model to the entire EuREC cohort found an almost perfect agreement between the predicted and observed risk factors (kappa 0.77, 95% CI 0.65 to 0.90). Conclusion Extensive coverage of intercostal arteries alone by a thoracic stent-graft is not associated with symptomatic SCI; however, simultaneous closure of at least 2 vascular territories supplying the spinal cord is highly relevant, especially in combination with prolonged intraoperative hypotension. As such, these results further emphasize the need to preserve the left subclavian artery during TEVAR.

Stent graft-induced new entry after endovascular repair for Stanford type B aortic dissection.

BACKGROUND Stent graft-induced new entry (SINE), defined as the new tear caused by the stent graft and excluding those arising from natural disease progression or iatrogenic injury from the endovascular manipulation, has been increasingly observed after thoracic endovascular aortic repair (TEVAR) for Stanford type B dissection in our center. SINE appears to be remarkably life threatening. We investigated the incidence, mortality, causes, and preventions of SINE after TEVAR for Stanford type B dissection. METHODS Data for 22 patients with SINE were retrospectively collected and analyzed from 650 patients undergoing TEVAR for type B dissection from August 2000 to June 2008. An additional patient was referred to our center 14 months after TEVAR was performed in another hospital. The potential associations of SINE with Marfan syndrome, location of SINE and endograft placement, and the oversizing rate were analyzed by Fisher exact probability test or t test. RESULTS We found 24 SINE tears in 23 patients, including SINE at the proximal end of the endograft in 15, at the distal end in 7, and at both ends in 1. Six patients died. SINE incidence and mortality reached 3.4% and 26.1%, respectively. Two SINE patients were diagnosed with Marfan syndrome, whereas there were only 6 Marfan patients among the 651 patients. The 16 proximal SINEs were evidenced at the greater curve of the arch and caused retrograde type A dissection. The eight distal SINEs occurred at the dissected flap, and five caused enlarging aneurysm whereas three remained stable. The endograft was placed across the distal aortic arch during the primary TEVAR in all 23 patients. The incidence of SINE was 33.33% among Marfan patients vs 3.26% among non-Marfan patients (P = .016). There was no significant difference in mortality between proximal and distal SINE (25% vs 28.6%, P > .99), incidence of SINE between endograft placement across the arch and at the straight portion of descending thoracic aorta (23 of 613 vs 0 of 38, P = .39), and the oversizing rate between SINE and non-SINE patients (13% ± 4.5% vs 16% ± 6.5%, P = .98). CONCLUSIONS SINE appears not to be rare after TEVAR for type B dissection and is associated with substantial mortality. The stress yielded by the endograft seems to play a predominant role in its occurrence. It is important to take this stress-induced injury into account during both design and placement of the endograft.

Treatment of symptomatic isolated dissection of superior mesenteric artery

OBJECTIVE To present the short- to midterm outcomes after management of 14 patients with symptomatic isolated dissection of superior mesenteric artery (SIDSMA) and propose a preliminary treatment algorithm. BACKGROUND SIDSMA is a rare but potentially fatal entity. However, most of these reports were isolated case reports, and a consensus treatment protocol remains lacking so far. It would be meaningful to propose a reasonable treatment algorithm for it. METHODS Patients with SIDSMA who were treated in our center between July 2007 and June 2011 were retrospectively collected and analyzed. Based upon the abdominal pain and signs, the clinical manifestations have been retrospectively classified into grade I (peritonitis absent) and grade II (peritonitis present). Medical treatment mainly included anticoagulation, antiplatelet, and bowel rest. Endovascular stent placement and surgical fenestration with exploratory laparotomy have been selected according to the grade classification. Computed tomographic angiography, magnetic resonance angiography, or duplex scans have been used for diagnosis and follow-up. RESULTS Fourteen consecutive patients with SIDSMA were collected; among them, 13 cases belonged to grade I and one to grade II. The mean duration from the onset to the admission was 12 ± 12 days (range, 0.5-45 days). The mean distance from the primary tear to the ostium of superior mesenteric artery (SMA) was 26 ± 4 mm (range, 15-32 mm). Medical treatment was given for 13 patients of grade I for the first 3 to 5 days after admission, and the abdominal pain remarkably or completely resolved in four patients who received continued medical treatment, whereas the other unresolved nine patients were converted to endovascular stent placement that succeeded in four and failed in five patients. Since these five cases were free from peritoneal signs, medical treatment was given again instead of an immediate surgical intervention, and ultimately achieved complete alleviation of abdominal pain within the following 1 week. The mean duration from the start of medical treatment to the alleviation of symptoms, including the continued medical treatment after the failed endovascular stent placement, was 8 ± 3 days (range, 4-12 days). The grade II patient underwent a successful emergency surgical SMA fenestration without bowel resection. Follow-up was accomplished in all 14 cases, ranging from 2 to 48 months (mean, 30 ± 15 months). No intestinal necrosis, morbidity, or mortality developed during hospitalization. During the follow-up, all patients were free from aneurysmal formation of SMA or chronic intestinal ischemia, and all stents remained patent. CONCLUSIONS For grade I SIDSMA, most cases might be successfully treated with medical therapy, and the endovascular stent placement appears to be an acceptable alternative if medical treatment fails. For grade II SIDSMA, the endovascular stenting combined with laparoscopic exploration and/or open surgery could be a reasonable option.

New insights regarding the incidence, presentation and treatment options of aorto-oesophageal fistulation after thoracic endovascular aortic repair: the European Registry of Endovascular Aortic Repair Complications

OBJECTIVES To review the incidence, clinical presentation, definite management and 1-year outcome in patients with aorto-oesophageal fistulation (AOF) following thoracic endovascular aortic repair (TEVAR). METHODS International multicentre registry (European Registry of Endovascular Aortic Repair Complications) between 2001 and 2011 with a total caseload of 2387 TEVAR procedures (17 centres). RESULTS Thirty-six patients with a median age of 69 years (IQR 56-75), 25% females and 9 patients (19%) following previous aortic surgery were identified. The incidence of AOF in the entire cohort after TEVAR in the study period was 1.5%. The primary underlying aortic pathology for TEVAR was atherosclerotic aneurysm formation in 53% of patients and the median time to development of AOF was 90 days (IQR 30-150). Leading clinical symptoms were fever of unknown origin in 29 (81%), haematemesis in 19 (53%) and shock in 8 (22%) patients. Diagnosis could be confirmed via computed tomography in 92% of the cases with the leading sign of a new mediastinal mass in 28 (78%) patients. A conservative approach resulted in a 100% 1-year mortality, and 1-year survival for an oesophageal stenting-only approach was 17%. Survival after isolated oesophagectomy was 43%. The highest 1-year survival rate (46%) could be achieved via an aggressive treatment including radical oesophagectomy and aortic replacement [relative risk increase 1.73 95% confidence interval (CI) 1.03-2.92]. The survival advantage of this aggressive treatment modality could be confirmed in bootstrap analysis (95% CI 1.11-3.33). CONCLUSIONS The development of AOF is a rare but lethal complication after TEVAR, being associated with the need for emergency TEVAR as well as mediastinal haematoma formation. The only durable and successful approach to cure the disease is radical oesophagectomy and extensive aortic reconstruction. These findings may serve as a decision-making tool for physicians treating these complex patients.

Association of smooth muscle cell phenotypes with extracellular matrix disorders in thoracic aortic dissection

OBJECTIVE Extracellular matrix dysregulation in the aortic media has been considered as the intrinsic factor for the formation of thoracic aortic dissection. However, the mechanisms of extracellular matrix disorders in the dissected aortic media remain unclear. This study was designed to investigate the relevance between smooth muscle cell phenotypes and extracellular matrix disorders in the dissected media. Their interaction may account for the pathogenesis of thoracic aortic dissection. METHODS AND RESULTS Thoracic aortic samples were collected from 10 patients with thoracic aortic dissection and 10 controls. Primary cultures of aortic medial smooth muscle cells were obtained with optimized explant technique. In this study, α-smooth muscle actin, smooth muscle myosin heavy chain 2, and smoothelin were applied as the contractile phenotypic markers and osteopontin was applied as the synthetic marker. Compared with controls, immunostaining and immunoblotting demonstrated that in vivo expression of α-smooth muscle actin, smooth muscle myosin heavy chain 2, and smoothelin were significantly decreased in the dissected media, whereas that of osteopontin was elevated (P<.01 for all). In vitro expression of the phenotypic markers showed the similar patterns. Furthermore, smooth muscle cells derived from the dissected media exhibited enhanced proliferation (P<.01), increased collagens I and III synthesis (2.6- and 4.4-fold, respectively; P<.01 for both), and elevated matrix metalloproteinase-2 production (4.2-fold; P<.01). Consistently, the protein levels of type I and III collagens and matrix metalloproteinase-2 in the dissected media were raised by 4.6-, 4.0-, and 3.7-fold, respectively (P<.01 for all). Collagen deposition was correspondingly increased and elastic fibers were decreased and disrupted. CONCLUSIONS Smooth muscle cells in the dissected media exhibit phenotypic switching from the contractile to the synthetic type. The synthetic smooth muscle cells increase collagen synthesis and matrix metalloproteinase-2 production, both of which can promote collagen deposition and elastin degradation in thoracic aortic dissection.

Stent fractures after superficial femoral artery stenting: risk factors and impact on patency.

Purpose: To determine the risk factors and clinical impact of stent fractures after superficial femoral artery (SFA) stenting. Methods: From May 2009 to June 2012, 171 consecutive patients (mean age 74.5±7.8, years; 106 men) who presented with SFA stenosis or occlusion in 205 limbs underwent stent implantation in the SFA at a single center. Stent fractures were determined by radiography and classified into types I through V. Loss of patency was assessed by duplex ultrasonography (>2.4 peak systolic velocity ratio) or angiography (percent diameter stenosis >50%). Results: The 12- and 24-month primary patency rates were 49.8% and 43.4%, respectively. Stent fractures occurred in 12.5% and 26.8% per limb (6.6% and 19.4% per stent) at 12 and 24 months, respectively. Primary patency was numerically worse in the stent fracture group but not statistically different from the group without fractures at 2 years. Primary patency for different classes of stent fracture were 30.8% (type I), 50.0% (type II), and 31.3% (type III–V). Hyperlipidemia (p=0.001), TransAtlantic Inter-Society Consensus II classification (p=0.007), chronic total occlusion (CTO; p<0.001), proximal lesion location (p=0.008), lesion calcification (p=0.025), total stent length (p=0.005), stent diameter (p=0.001), and number of stents (p=0.001) were statistically significant predictors of stent fracture. Multivariate analysis showed that CTO (hazard ratio 0.173, 95% confidence interval 0.042 to 0.716, p=0.015) was an independent predictor of stent fracture. Conclusion: Stent fractures occur more frequently in patients with CTOs after treatment of longer stented lesions. Although multivariate analysis showed that CTO was the only independent predictor regardless of stent length or number, the stent fracture rate was numerically higher in the severe calcification and proximal SFA lesion subgroups. Stent fracture did not appear to affect long-term patency rates, but this is yet to be confirmed with further follow-up.

The rhythmic expression of clock genes attenuated in human plaque-derived vascular smooth muscle cells

BackgroundAcute myocardial infarction and stroke are more likely to occur in the early morning. Circadian pacemakers are considered to be involved in the process. Many peripheral tissues and cells also contain clock systems. In this study, we examined whether the primary cultured human plaque-derived vascular smooth muscle cells (VSMCs) process circadian rhythmicity; furthermore, we investigated the expression difference of clock genes between normal human carotid VSMCs and human plaque-derived VSMCs.MethodsFifty-six human carotid plaques provided the atherosclerotic tissue, and 21 samples yielded viable cultured primary VSMCs. The normal carotid VSMCs were cultured from donors’ normal carotids. The mRNA levels of the target genes were measured by Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR).ResultsAfter serum shock, both types of cells showed clear circadian expressions of Bmal1, Cry1, Cry2, Per1, Per2, Per3 and Rev-erbα mRNA; meanwhile the Clock mRNA show a rhythmic expression in plaque-derived SMCs but not in normal carotid VSMCs. The expression levels of these main clock genes were significantly attenuated in human plaque-derived VSMCs compared with normal human carotid VSMCs. The rhythm of Bmal1 mRNA in plaque-derived VSMCs was changed.ConclusionThe present results demonstrate that the human plaque-derived VSMCs possess different circadian rhythmicity from that of normal carotid VSMCs. The rhythm changes of clock genes in plaque-derived VSMCs may be involved in the process of atherosclerosis and finally promote the rupture of plaque.

Transplantation of purified CD34+ cells in the treatment of critical limb ischemia.

BACKGROUND This study investigated the feasibility, safety, and efficacy of the intramuscular injection of CD34+ cells isolated from peripheral blood mononuclear cells (PB-MNCs) mobilized by granulocyte colony-stimulating factor (G-CSF) for the management of patients with critical limb ischemia (CLI) who were considered unlikely to have successful long-term revascularization with open bypass or endovascular methods. Cell therapy represents a new treatment modality for this subgroup of patients with CLI. To date, bone marrow or PB-MNCs have usually been used for transplantation. The current pilot study investigated whether the transplantation of purified CD34+ cells only would be competent in ischemia relief and limb salvage. METHODS From May 2009 to July 2011, 25 patients (mean age, 44 ± 12 years) were enrolled, and 25 lower extremities and three upper extremities were treated. After subcutaneous administration of G-CSF for 5 days at a dose of 5 to 10 μg/kg, apheresis and immunomagnetic separation were performed to acquire the isolated CD34+ cells, which were then intramuscularly injected into the ischemic sites. The patients were divided into three groups: low-dose, 10(5)/kg; medium-dose, 5 × 10(5)/kg; and high-dose, 10(6)/kg. The overall outcomes among all patients and the comparison among the groups were evaluated. RESULTS During the follow-up of 6 to 33 months, the overall outcomes showed that the Wong-Baker FACES pain rating scale score (WFPRSS) decreased from 7 ± 2 to 3 ± 3 (P < .001) and 1 ± 2 (P < .001) at 1 and 2 months, respectively; at 3 and 6 months, respectively, the peak pain-free walking time increased from 4 ± 3 to 13 ± 7 (P < .001) and 18 ± 6 minutes (P < .001), the ankle-brachial index increased from 0.46 ± 0.21 to 0.60 ± 0.17 (P = .003) and 0.67 ± 0.15 (P = .001), and the transcutaneous partial oxygen pressure increased from 27 ± 10 to 41 ± 11 (P < .001) and 55 ± 12 mm Hg (P < .001). Ulcers were healed in 10 of the 14 patients; four patients required above-knee or below-knee amputation ≤ 3 months. The Kaplan-Meier estimate of the rate of freedom from major amputation at 6 months was 84% (95% confidence interval, 63%-94%). The comparison among the three groups (low-dose, 5; medium-dose, 11; high-dose, 9) revealed no significant difference, except that the WFPRSS improvement at 1 month from baseline in the high-dose group (6.3 ± 1.7) was significantly superior to that in the low-dose (3.2 ± 3.3; P = .0487) and medium-dose (3.7 ± 2.8; P = .0352) groups. CONCLUSIONS Transplantation of CD34+ cells isolated from G-CSF-mobilized PB-MNCs appears to be feasible and safe, showing encouraging outcomes in the treatment of CLI patients who appear to have compromised options for long-term revascularization.

Polymorphisms in MMP-9 and TIMP-2 in Chinese patients with varicose veins.

BACKGROUND Varicose veins (VVs), a common vascular disease, are functionally characterized by dilation and tortuosity and are widely prevalent in the adult population. The pathophysiology and molecular mechanism of VVs are still unclear. A genetic risk for VVs has been demonstrated, although no genetic variant pertaining to VVs has been identified. Matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs), which can prevent excessive extracellular matrix (ECM) degradation, greatly impact vascular remodeling and may play a vital role in patients with VVs. We evaluated a potential association between polymorphisms in the promoters of MMP-9 and TIMP-2 and the risk for VVs in the Chinese population. MATERIALS AND METHODS Genotyping of the promoter region polymorphisms -1562C/T in MMP-9 and -418G/C in TIMP-2 was performed with PCR and restriction fragment length polymorphism (PCR-RFLP) assays with a group of 60 patients with VVs and 60 healthy controls. Purified PCR products were sequenced. RESULTS A significant correlation was found between patients with VVs and controls at -1562C/T in MMP-9. The TIMP-2 gene polymorphism -418G/C was also associated with VVs. CONCLUSIONS Our results suggest that polymorphisms in the promoter region of MMP-9 and TIMP-2 are associated with VVs in the Chinese population.

Use of a vascular occluder to treat a re-entry tear in a patient with stanford type B aortic dissection: acute and 1-year results.

Purpose: To evaluate the feasibility and efficacy of a vascular occluder to treat a patent re-entry tear near a visceral artery after stent-graft repair of Stanford type B aortic dissection. Case Report: A 34-year-old woman with a history of stent-graft repair for aortic dissection 6 months ago was admitted complaining of recurrent chest discomfort for 1 month. Computed tomographic angiography (CTA) revealed a proximal type I endoleak and a patent re-entry tear above the celiac artery orifice. A double-disk vascular occluder was used to treat the re-entry tear. The device was deployed successfully without perioperative complications; the re-entry tear was closed and perfusion of adjacent vessels was not compromised. CTA at 3 months and 1 year documented thrombus formation in the false lumen, proper position of the occluder, and no re-entry tear. Conclusion: It is feasible to treat patent re-entry tears with a vascular occluder after primary proximal stent-graft repairs. Long-term clinical efficacy has yet to be confirmed.