Clinical Study Of Therapeutic Strategies For Congenital Aortic Sinus Aneurysm Rupture And Proteomic Analysis Of Atrial Fibrillation Stroma In Different Canine Models Of Atrial Fibrillation

Objectives:Surgical intervention is the main treatment for a ruptured congenital sinus of Valsalva aneurysm(SVA).However,reports on the surgical experience are scarce.The postoperative progression of aortic regurgitation(AR)following SVA repair would increase the risk of reoperation which decreases the long-term survival.Thus,identifying the risk factors for postoperative AR progression is of great significance.Moreover,percutaneous closure of ruptured SVA has been becoming an alternative to the traditional surgical repair recently.However,the reports regarding direct comparison of these two treatment options are also scarce.In this study,we retrospectively analyzed the cases of our center to summarize our 10-year experience.A direct comparison was conducted to investigate whether percutaneous closure is as safe and effective as surgery repair.Methods:We reviewed the patients who diagnosed with a congenital ruptured SVA and underwent surgical repair in our center.Necessary data in the institutional database were extracted.Follow-up data were obtained from outpatient department records and telephone calls.Kaplan-Meier survival analysis was conducted to evaluate long-term results of surgical repair.The perioperative and follow-up assessment of aortic valve by transthoracic echocardiography were also obtained.The aortic regurgitation progression was grouped into three categories,including "newly developing","recurrence" and"worsening".A total of 16 variables were screened to identify potential risk factors by univariate Logistic regression analysis or Chi-Square test.Variables with P values of less than 0.1 were further analyzed by multivariable Logistic regression models to find independent risk factors.In addition,26 patients undergoing percutaneous closure were compared with 108 patients being treated surgically.To reduce the potential bias,32 patients from Surgical Repair group were selected by propensity score matching to form Matched group.Results:All the ruptured SVAs were successfully closed in patients being treated with surgical repair or percutaneous closure.The right coronary sinus was the most common origin of SVA.The most common associated deformities were a ventricular septal defect,aortic valve regurgitation and tricuspid regurgitation.In our institute,the majority of SVA defects were closed by patching.Only a small part of defects were repaired by direct suturing.SVA can be repaired through an incision of the cardiac chamber involved or a transaortic approach.Most of the patients were discharged at New York Heart Association functional class ? or ?.No severe procedure-related complications were found in the perioperative period.The incidence rate of short-term complications was satisfactory.The estimated 10-year survival rate was greater than 90%according to the Kaplan-Meier survival curve.After the univariate analysis,SVA originating from the right coronary sinus,coexisting with ventricular septal defect,larger diameter of aortic annulus and larger cardiothoracic ratio were screened as the potential risk factors.The multivariate analysis indicated that coexisting with ventricular septal defect(VSD)(OR:2.82,95%CI:1.217-6.532,P=0.016)and larger cardiothoracic ratio(OR:1.061,95%CI:1.001?1.124,P=0.047)were independent risk factors for postoperative AR progression.The median postoperative hospital stays of Matched group were significantly longer than that of Percutaneous Closure group(7 days vs.1 day,P<0.001).Aortic regurgitation,residual shunt and recurrence of SVAs were common complications in both Percutaneous Closure group and Surgical Repair group.Conclusions:Surgical repair is an effective and safe treatment for a ruptured SVA.The vast majority of patients who undergo surgical repair can survive for a long time.More careful inspection and appropriate surgical techniques are necessary for patients coexisting with VSD or with larger cardiothoracic ratio to prevent postoperative AR progression after surgical repair.The appropriately selected patients with ruptured SVA could be treated by percutaneous closure with an acceptable risk of short-term complications.Though surgical repair remains the main treatment option for ruptured SVAs,percutaneous closure could be considered in patients with a small-size rupture and no associated cardiac abnormalities.Background:Atrial fibrillation(AF)is a common cardiac arrhythmia worldwide.The various aetiological factors provide different substrates for trigger and maintenance of AF.Canine AF models are widely used for studying AF mechanisms.We established three AF animal models using two methods and performed a proteomic analysis of tissues from the left atrium to compare the molecular profiling between different AF substrates.Methods:A total of 18 Beagle's dogs were divided into four groups(CTRL,MR,RAP and MR+RAP group).Atrial rapid pacing and/or mitral regurgitation were established on animals.The models were monitored by echocardiography and Insertable Cardiac Monitors.Tissues from the left atrium were collected for histological and proteomic analysis.Hematoxylin and eosin(H&E)stain and Masson's trichrome stain were performed on paraffin sections.Differentially expressed proteins(DEPs)were identified by fold change and FDR.Hierarchical clustering analysis and enrichment analysis were conducted.Protein-Protein interaction(PPI)networks of the DEPs were also developed.The results of proteomics were validated by Western Blot.Results:All dogs successfully developed AF in each group.However,histological analysis by Masson's trichrome stain showed no significant fibrosis in MR,RAP or MR+RAP groups.Compared with CTRL group,5,72 and 521 proteins were identified as DEPs in MR,RAP and MR+RAP group,respectively.Hierarchal clustering analysis revealed that each of MR,RAP and MR+RAP group can be successfully distinguished with CTRL group by DEPs.GO enrichment and KEGG pathway enrichment analysis were conducted.Several GO terms and pathways were identified for each group.The networks of DEPs were generated after PPI analysis.A few hub genes(proteins)were also distinguished.Conclusions:Proteomic analysis of tissues from the left atrium revealed that different canine atrial fibrillation models had different protein expression profiling.Enrichment analysis suggested that the dysfunction of mitochondrial function and energy metabolism were a common biological process in different canine models of atrial fibrillation.