Xiangyang Qian

Hybrid total arch repair without deep hypothermic circulatory arrest for acute type A aortic dissection (R1).

OBJECTIVE To investigate the surgical outcomes of hybrid total arch repair without deep hypothermic circulatory arrest for patients with acute Stanford type A aortic dissection. METHODS Retrospective review of clinical data of patients with acute Stanford type A aortic dissection who underwent surgical repair at our institution between November 2009 and December 2011 identified 21 patients who underwent hybrid total arch repair without deep hypothermic circulatory arrest. The in-hospital and follow-up data were investigated. Postoperative serial computed tomography angiography was used to evaluate the fate of true and false lumen in arch and descending aorta. RESULTS Mean follow-up was 13.8 months (range, 3 to 21 months). The 1- and 12-month survival rates (by Kaplan-Meier analysis) were 95.2% (95% confidence interval, 86.2%-100%) and 90.5% (95% confidence interval, 78.0%-100%), respectively. No endograft caudal migration occurred. One patient with type I endoleak was successfully resolved during operation. There was no late rupture or paraplegia. CONCLUSIONS Hybrid total arch repair without deep hypothermic circulatory arrest offers a promising alternative to risk reduction of complications during the postoperative period and late adverse events resulting from false lumen enlargement in the arch and descending aorta.

Angiotensin II increases matrix metalloproteinase 2 expression in human aortic smooth muscle cells via AT1R and ERK1/2.

Increased levels of angiotensin II (Ang II) and activated matrix metalloproteinase 2 (MMP-2) produced by human aortic smooth muscle cells (human ASMCs) have recently been implicated in the pathogenesis of thoracic aortic aneurysm (TAA). Additionally, angiotensin II type 1 receptor (AT1R)-mediated extracellular signal-regulated kinase (ERK)1/2 activation contributes to TAA development in Marfan Syndrome. However, there is scant data regarding the relationship between Ang II and MMP-2 expression in human ASMCs. Therefore, we investigated the effect of Ang II on MMP-2 expression in human ASMCs and used Western blotting to identify the Ang II receptors and intracellular signaling pathways involved. Reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence data demonstrated that Ang II receptors were expressed on human ASMCs. Additionally, Ang II increased the expression of Ang II type 2 receptor (AT2R) but not AT1R at both the transcriptional and translational levels. Furthermore, Western blotting showed that Ang II increased MMP-2 expression in human ASMCs in a dose- and time-dependent manner. This response was completely inhibited by the AT1R inhibitor candesartan but not by the AT2R blocker PD123319. In addition, Ang II–induced upregulation of MMP-2 was mediated by the activation of ERK1/2, whereas p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK) had no effect on this process. In conclusion, these results indicate that Ang II can increase the expression of MMP-2 via AT1 receptor and ERK1/2 signaling pathways in human ASMCs and suggest that antagonists of AT1R and ERK1/2 may be useful for treating TAAs.

One-stage repair of extensive aortic aneurysms: mid-term results with total or subtotal aortic replacement

OBJECTIVES To retrospectively analyse the mid-term clinical results of one-stage repair of extensive aortic aneurysms with total or subtotal aortic replacement. METHODS From February 2004 to February 2011, 21 patients with extensive aortic aneurysm underwent one-stage total or subtotal aortic replacement for aortic dissection (95.23%) or aortic aneurysms. Operations were performed under circulatory arrest with profound hypothermia. Patients were opened with a mid-sternotomy and a thoraco-abdominal incision. Extracorporeal circulation was instituted as usual. During cooling, the ascending aorta or aortic root was replaced. At the nasopharyngeal temperature of 20°C, the aortic arch was replaced with selective antegrade cerebral perfusion. Staged aortic occlusions allowed for replacement of the descending thoracic and abdominal aorta. T6 to T12 intercostal arteries and L1,L2 lumbar arteries were formed to a neo-intercostal artery in place and were connected to an 8-mm branch for maintaining spinal cord blood perfusion. Visceral arteries were joined into a patch and anastomosed to the end of the main graft. RESULTS The early mortality was 4.8% (1 of 21); 1 patient died due to renal failure and multiple organ failure. No patient had spinal cord deficits postoperatively. Two patients had postoperative stroke at Day 5 and 7, respectively. Twenty patients were all alive with good life status during the follow-up period ranging from 18 to 84 months postoperatively. One patient was reoperated with aortic valve replacement because of massive valve insufficiency after 2 years. During the follow-up period, reconstructed intercostal arteries were clogged in 3 patients and dilatated in 2 patients with Marfan syndrome. CONCLUSIONS One-stage repair of extensive aortic aneurysms with total or subtotal aortic replacement is safe and effective. It is feasible with acceptable surgical risks and satisfactory results. It can eliminate the risk of remnant aortic aneurysm rupture in staged total aortic replacement and has satisfactory mid-term results.

Angiotensin II Induces an Increase in Matrix Metalloproteinase 2 Expression in Aortic Smooth Muscle Cells of Ascending Thoracic Aortic Aneurysms Through JNK, ERK1/2, and p38 MAPK Activation.

Abstract: In this study, we hypothesized that angiotensin II (Ang II) induces matrix metalloproteinase 2 (MMP-2) upregulation in aneurysmal smooth muscle cells (ASMCs) derived from ascending thoracic aortic aneurysms (ATAAs). We compared MMP-2 protein levels in ascending aortic specimens using Western blot and plasma concentrations by enzyme-linked immunosorbent assay between ATAA (n = 40) and coronary heart disease patients (n = 40). Additionally, the protein level of angiotensinogen (AGT) in the ascending aorta and the plasma concentration of Ang II were detected by Western blot and radioimmunoassay, respectively, in ATAA and coronary heart disease patients. In ATAA patients, Ang II and MMP-2 plasma levels were significantly increased (P < 0.05). Additionally, AGT and MMP-2 protein levels in the aorta of ATAA patients were higher (P < 0.01). Enhanced AGT suggested that the amount of Ang II in aneurysmal aorta specimens may be also increased, which was confirmed by immunofluorescent staining for Ang II. Moreover, we investigated the effect of Ang II on MMP-2 upregulation by ASMCs and determined the Ang II receptors and intracellular signaling pathways that are involved. Our results showed that treatment with Ang II significantly increased the expression of MMP-2 through the Ang II type 1 receptor (AT1R) and activated the 3 major mitogen-activated protein kinases (MAPKs), JNK, ERK1/2, and p38 MAPK. In conclusion, these results indicate that Ang II can induce MMP-2 expression elevation through AT1R and MAPK pathways in ASMCs and suggest that there is therapeutic potential for angiotensin receptor blocker drugs and MAPK inhibitors in the prevention and treatment of ATAAs.

Angiotensin II induces an increase in MMP-2 expression in idiopathic ascending aortic aneurysm via AT1 receptor and JNK pathway

The cellular and molecular mechanisms responsible for human idiopathic ascending aortic aneurysm (IAAA) remain unknown. Matrix metalloproteinase-2 (MMP-2) is a key enzyme for the degradation of extracellular matrix in aneurysmal walls. The aim of this study was to elucidate the role of the angiotensin II (Ang II) pathway in MMP-2 induction in IAAA aortic walls. Quantitative polymerase chain reaction and western blot analysis were used to compare the MMP-2 mRNA and protein levels in ascending aortic specimens with those in IAAA patients (n = 10) and heart transplant donors (n = 5) without any aortopathy. It was found that MMP-2 expression was significantly increased, which was associated with elastic lamellae disruption in IAAA walls. Additionally, the expression levels of angiotensinogen (AGT) and Ang II in the ascending aortic tissues from individuals with and without IAAAs were detected by western blot analysis and radioimmunoassay, respectively. The results demonstrated that the expressions of AGT and Ang II protein were significantly increased in the ascending aortic tissues of IAAA patients. Furthermore, whether Ang II induces MMP-2 expression was investigated using human IAAA walls ex vivo culture. It was found that exogenous Ang II increased the MMP-2 expression in a dose-dependent manner, which was completely inhibited by the Ang II type 1 receptor (AT1R) inhibitor candesartan and was mediated by c-Jun N-terminal kinase (JNK) activation. Taken together, these results indicate that Ang II can induce an increase of MMP-2 expression via AT1R and JNK in ex vivo cultured IAAA aortic walls, and suggest that angiotensin receptor blocker (ARB) drugs and JNK inhibitors have the potential in the prevention or treatment of IAAAs.

Genetic testing of the FBN1 gene in Chinese patients with Marfan/Marfan-like syndrome.

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder typically involving the ocular, skeletal and cardiovascular systems, and aortic aneurysms/dissection mainly contributes to its mortality. Here, we performed genetic testing of the FBN1 gene in 39 Chinese probands with Marfan/Marfan-like syndrome and their related family members by Sanger sequencing. In total, 29 pathogenic/likely pathogenic FBN1 mutations, including 17 novel ones, were identified. In addition, most MFS patients with aortic disease (62%) had a truncating or splicing mutation. These results expand the FBN1 mutation spectrum and enrich our knowledge of genotype-phenotype correlations. Genetic testing for MFS and its related aortic diseases is increasingly important for early intervention and treatment.

Early and mid-term results after hybrid total arch repair of DeBakey type I dissection without deep hypothermic circulatory arrest.

OBJECTIVES The purpose of this study was to assess the efficacy of the hybrid total arch procedure for the treatment of DeBakey type I dissection by analyzing mid-term results. METHODS From November 2009 to September 2014, 56 patients with DeBakey type I dissection underwent hybrid total arch repair without deep hypothermic circulatory arrest. During the follow-up, computed tomographic imaging was performed to evaluate the aortic diameter, true lumen diameter, false lumen diameter and false patency at the following three levels: pulmonary bifurcation, diaphragm and superior mesenteric artery. RESULTS The hospital mortality rate was 3.6% (2/56 patients). Three patients exhibited type Ia endoleak during the operation and 1 patient demonstrated type II endoleak 5 days after surgery. During the follow-up, false lumen complete thrombosis was observed at the level of the pulmonary bifurcation in 94% of patients (P < 0.001). At the level of the diaphragm and superior mesenteric artery, false lumen thrombosis was observed in 68% (P < 0.001) and 36% (P < 0.001) of patients, respectively. No patient had type I or III endoleak and no reoperation was related to residual dissected aorta. The actuarial 1-, 3- and 5-year survival rates were 96.4% [95% confidence interval (95% CI), 91.5-100], 92.3% (95% CI, 85-99.6) and 89.6% (95% CI, 80.8-98.4), respectively. CONCLUSIONS For patients with DeBakey type I dissection, the hybrid total arch procedure can be safely adopted with good mid-term results and with low morbidity and mortality. Longer-term follow-up is required to confirm the viability of this technique.

Acute Kidney Injury after Total Arch Replacement Combined With Frozen Elephant Trunk Implantation: Incidence, Risk Factors, and Outcome

OBJECTIVES Acute kidney injury (AKI) is common after thoracic aortic surgery and is a significant predictor of morbidity and mortality. Total arch replacement (TAR) combined with frozen elephant trunk (FET) implantation has been reported to produce satisfactory clinical outcomes, whereas several features of the surgical procedure may induce postoperative AKI. The authors aimed to clarify the incidence of and risk factors for postoperative AKI and the association of AKI with short-term outcomes. DESIGN This study was a retrospective analysis of a prospectively collected cohort. A multivariate logistic regression model was used to identify predictors of postoperative AKI. SETTING Single center. PARTICIPANTS Clinical data were analyzed for 553 consecutive patients who underwent TAR combined with FET implantation between 2013 and 2016. INTERVENTIONS None MEASUREMENTS AND MAIN RESULTS: Postoperative AKI was defined using the Kidney Disease Improving Global Outcomes criteria. Postoperative AKI occurred in 77.6% of the whole cohort. Patients in stage 3 AKI were associated with a higher incidence of major adverse events and in-hospital and 90-day mortality (p < 0.001, p < 0.05, p < 0.01, respectively). In the multivariate analysis, male sex (odds ratio [OR] 1.94; 95% confidence interval [95% CI] 1.22-3.18; p = 0.005); older age (per 10 years) (OR 1.37; 95% CI 1.14-1.67; p = 0.001); elevated body mass index (per 5 kg/m2) (OR 1.41; 95% CI 1.08-1.87; p = 0.01); and prolonged cardiopulmonary bypass duration (per 30 minutes) (OR 1.17; 95% CI 1.01-1.37; p = 0.03) were identified as independent predictors of postoperative AKI. CONCLUSION TAR combined with FET implantation carries a high-risk for postoperative AKI compared with other types of thoracic aortic surgeries. Cardiopulmonary bypass duration was identified as the only modifiable predictor of AKI, and patients may benefit from moderate hypothermic circulatory arrest instead of deep hypothermic circulatory arrest.

In-hospital major adverse outcomes of acute Type A aortic dissection

OBJECTIVES Acute Type A aortic dissection exhibits poor in-hospital outcomes after emergency surgery. Evaluation of risk predictors for in-hospital major adverse outcomes (MAO) is key to reducing the mortality rate and improving the quality of care. METHODS We enrolled 70 patients who presented with postoperative MAO and 195 patients who recovered well. Through univariate and multivariate analyses, clinical characteristics were compared between the patients in the 2 groups. RESULTS In-hospital mortality was 6.4% in this series. The patients in the MAO group were older and had a higher frequency of coronary artery involvement by dissection (60.0% vs 21.0%) (P < 0.05). Preoperatively, when compared to the group of patients without MAO, the patients in the MAO group were more likely to have a neurological deficit (18.6% vs 9.7%) and, to a certain extent, lower limb symptoms encompassing visceral and renal malperfusion (20.0% vs 8.2%) (P < 0.05). Compared to patients with MAO, patients without MAO experienced longer duration from initial onset of symptoms to surgery and had an ascending aorta with a larger diameter. In patients with MAO, the average durations of cardiopulmonary bypass (CPB), cardiac arrest and hypothermic circulatory arrest were much longer than those in patients with no MAO (all P < 0.001). Multivariate analysis showed that in-hospital adverse outcomes were associated with older age [odds ratio (OR) = 1.047 (1.008-1.087), P < 0.05], presentation of lower limb symptoms prior to surgery [OR = 2.905 (1.109-7.608), P < 0.05] and long CPB duration [OR = 1.011 (1.005-1.018), P < 0.01]. When patients with acute Type A aortic dissection experienced a duration from symptom onset to surgery [OR = 0.993 (0.987-0.999), P < 0.05] or had an ascending aorta with a large diameter [OR = 0.942 (0.892-0.995), P < 0.05], the number of postoperative adverse events decreased significantly. CONCLUSIONS At a centre that has a large caseload, where practitioners can become proficient through experience as well as training, good outcomes can be dependably produced in patients with acute Type A aortic dissection and without malperfusion syndromes. For patients presenting with these risk features, MAO need to be anticipated, and the incidence of a composite end point of major adverse events remains unsatisfactory.

Aortic Surgical Emergencies in Young Children With Loeys-Dietz Syndrome.

Loeys-Dietz syndrome presents early in life with rapidly progressive aortic aneurysmal disease. Aortic emergency in young children with Loeys-Dietz syndrome is an extremely rare occurrence. In this communication we report on 2 young children whose diagnoses were missed and consequently underwent urgent aortic repair due to aortic emergencies. For personalized management of aortic disease in Loeys-Dietz syndrome patients, when and how do we intervene?