Daqiao Guo

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.

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.

Predictors and treatments of Proglide-related complications in percutaneous endovascular aortic repair.

Purpose To investigate the predictors and treatment of the 6-Fr Perclose Proglide-related complications (PRC) in percutaneous endovascular aortic repair (pEVAR). Methods We retrospectively analyzed the PRC after pEVAR for the treatment of aortic aneurysm or dissection in our center from December 2012 to November 2013. Procedure success was defined as effective functioning of the two devices and local hemostasis. Access-related adverse events included vascular complications and device failures. Operative data and angiographic and computed tomography images were collected to assess the complications and treatment strategy. Results A total of 198 patients with 275 puncture sites underwent pEVAR with the 6-Fr Perclose Proglide. The procedure was successful in 178 patients (89.9%), whereas PRC occurred in 20 cases (10.1%), including 10 device failures and 10 vascular complications. An extra manual ancillary compression was conducted in 7 patients, one more device was used in 8 patients, and surgical repair of the femoral artery was performed in 5 patients. PRC had a tendency to occur in patients with body mass index (BMI)>30 kg/m2 (p = 0.021), thoracic stent grafts (p = 0.038), common femoral artery (CFA) calcification (p = 0.001), CFA depth>4 cm (p = 0.001), and sheath size>20Fr (p = 0.005). Device failure-related mortality was zero. None of the access sites had complications during the midterm follow-up. Conclusions The pre-close technique with 6-Fr Perclose Proglide devices for pEVAR appears to be safe and effective with low technical failure and complication rates. Careful patient selection and proficiency in device manipulation might reduce the device related complications.

Patients carrying CYP2C19 loss of function alleles have a reduced response to clopidogrel therapy and a greater risk of in-stent restenosis after endovascular treatment of lower extremity peripheral arterial disease

OBJECTIVE This study evaluated the relationship between the cytochrome P450 (CYP) 2C19 genotype and the antiplatelet effect of clopidogrel therapy and investigated whether genotyping can predict the risk of ischemic events after endovascular treatment (ET) of lower extremity peripheral arterial disease. METHODS From January 2011 to July 2012, 120 consecutive patients with arteriosclerosis obliterans (TransAtlantic Inter-Society Consensus for the Management of Peripheral Arterial Disease [TASC II] A-C) in the superficial femoral artery were included in a prospectively maintained database. Patients received 75 mg clopidogrel and 100 mg aspirin daily for at least 5 days before TaqMan (Life Technologies, Grand Island, NY) of CYP2C19 single-nucleotide polymorphisms and thromboelastography of the clopidogrel response. ET was subsequently performed, and follow-up evaluations, including duplex ultrasound imaging and ankle-brachial index assessment, were performed at 1, 3, 6, and 12 months after ET. During the follow-up, stent patency was assessed by ultrasound imaging, computed tomography angiography, or digital subtraction angiography. RESULTS A total of 74 ET procedures were performed. Fifty of the enrolled patients (41.7%) completed the follow-up examinations and were included in the analysis. The mean duration of follow-up was 9.8 ± 2.1 months (range, 1-30 months). Carriers of at least one CYP2C19 loss-of-function (LOF) allele had a diminished pharmacodynamic response to clopidogrel (51.6 ± 20.1 vs. 39.8 ± 15.2 for patients without and with LOF alleles, respectively; P = .022). Carriers of one LOF allele had an increased incidence of ischemic events compared with patients without any LOF alleles (59.0% vs. 20.8%, respectively; P = .008). This trend was even more evident in patients with two LOF alleles compared with patients with no LOF alleles (100% vs. 20.8% ischemic events; P = .002). The cumulative primary patency rate at 12 months was 56.0%, with significant differences between groups (73.1% vs. 34.6% in patients without and with LOF alleles, respectively; P = .0.006). CYP2C19 LOF carrier status was associated with an increased rate of primary end points (P = .007). On the basis of their adenosine diphosphate-induced platelet aggregation, patients with high platelet reactivity had a significantly higher risk of ischemic events (P = .012). CYP2C19 genotypic classification (adjusted hazard ratio, 2.688; 95% confidence interval, 1.366-5.288; P = .004) and history of smoking (adjusted hazard ratio, 2.430; 95% confidence interval, 1.024-5.765; P = .044) were independent risk factors for ischemic events. CONCLUSIONS CYP2C19 LOF alleles were associated with a diminished platelet response to clopidogrel treatment. Patients carrying CYP2C19 LOF alleles who are treated with clopidogrel may trend toward a poor prognosis after ET.

Coverage of the left subclavian artery without revascularization during thoracic endovascular repair is feasible: a prospective study.

BACKGROUND To effectively isolate thoracic aortic lesions in thoracic endovascular aortic repair (TEVAR), an adequate proximal landing zone length is required. The left subclavian artery (LSCA) and other branches of the aortic arch commonly impose limitations on proximal landing zone length, restricting the use of TEVAR. In this study, we investigated the outcomes of LSCA coverage during TEVAR. METHODS Between March 2009 and February 2010, we recruited patients with thoracic dissection, aneurysm or trauma from a single center for TEVAR. We categorized patients into 3 groups: full coverage, partial coverage, or noncoverage of the LSCA. We measured pre- and postoperative blood pressures and evaluated complications during follow-up. RESULTS We recruited 111 patients for our study: 55 (50%) and 25 (23%) patients had full and partial LSCA coverage, respectively. The upper left arm blood pressures before and after the operations were significantly different between the full-coverage group and the other groups (P < 0.0001). Follow-up occurred between 6 and 20 months, and the mean follow-up time was 10.4 months. Thirteen patients (24%) in the full-coverage group and 2 patients (8%) in the partial-coverage group suffered from simple vertebrobasilar ischemia (VBI). Eleven of the patients with VBI (20%) in the full-coverage group and 2 (8%) patients with VBI in the partial-coverage group had left subclavian steal syndrome at follow-up. No paraplegia or stroke was observed. CONCLUSIONS Intentional coverage of the LSCA to obtain an adequate proximal landing zone for TEVAR can be a treatment option for thoracic aortic lesions, although some patients experienced mil complications.

hCLOCK Causes Rho-Kinase-Mediated Endothelial Dysfunction and NF-κB-Mediated Inflammatory Responses

Background. The human Circadian Locomotor Output Cycle protein Kaput (CLOCK) gene was originally discovered as a regulator of essential human daily rhythms. This seemingly innocuous gene was then found to be associated with a multitude of human malignancies, via several biochemical pathways. We aimed to further investigate the role of hCLOCK in the hypoxia-oxidative stress response system at the biochemical level. Methods. Expression levels of Rho GTPases were measured in normoxic and hypoxic states. The effect of hCLOCK on the hypoxic response was evaluated with the use of a retroviral shRNA vector system, a Rho inhibitor, and a ROS scavenger by analyzing expression levels of hCLOCK, Rho GTPases, and NF-κB pathway effectors. Finally, in vitro ROS production and tube formation in HUVECs were assessed. Results. Hypoxia induces ROS production via hCLOCK. hCLOCK activates the RhoA and NF-κB signaling pathways. Conversely, inhibition of hCLOCK deactivates these pathways. Furthermore, inhibition of RhoA or decreased levels of ROS attenuate these pathways, but inhibition of RhoA does not lead to decreased levels of ROS. Overall findings show that hypoxia increases the expression of hCLOCK, which leads to ROS production, which then activates the RhoA and NF-κB pathways. Conclusion. Our findings suggest that hypoxic states induce vascular oxidative damage and inflammation via hCLOCK-mediated production of ROS, with subsequent activation of the RhoA and NF-κB pathways.