Zhigang Song

Genetic polymorphisms of glutathione S-transferase genes GSTM1, GSTT1 and risk of coronary heart disease

To clarify the role of glutathione S-transferases (GSTs; GSTM1 and GSTT1) status in susceptibility to coronary heart disease (CHD), a meta-analysis of published studies was performed. A total of 19 studies including 8020 cases and 11 501 controls were included in this meta-analysis. In a combined analysis, the relative risks for CHD of the GSTM1 null and GSTT1 null polymorphisms were 1.47 [95% confidence interval (CI): 1.08-2.01] and 1.26 (95% CI: 0.90-1.75), respectively. Three potential sources of heterogeneity including ethnicity, source of control and sample size of study were also assessed. However, no significant association was found in stratified analyses. By pooling data from eight studies (2909 cases and 3745 controls) that considered combinations of GSTT1 and GSTM1 genotypes, a statistically significant increased risk for CHD [odds ratio (OR = 2.38, 95% CI: 1.03-5.48)] was detected for individuals with combined deletion mutations in both genes compared with positive genotypes. Results from the meta-analysis of five studies on GSTs stratified according to smoking status showed an increased risk for individuals with null genotype (OR = 2.21, 95% CI: 1.24-3.92 for GSTM1 and OR = 3.29, 95% CI: 1.49-7.26 for GSTT1) versus non-null genotypes. This meta-analysis suggests that the GSTM1 null genotype may slightly increase the risk of CHD and that interaction between unfavourable GSTs genotypes may exist.

MicroRNA-30b is a multifunctional regulator of aortic valve interstitial cells

OBJECTIVE Calcific aortic valve disease is an active process involving a wide range of pathologic changes. Valve interstitial cells are the most prevalent cells in the heart valve and maintain normal valve structure and function. MicroRNAs (miRNAs) are essential posttranscriptional modulators of gene expression, and miRNA-30b is a known repressor of bone morphogenetic protein 2-mediated osteogenesis. We hypothesized that miRNA-30b is a multifunctional regulator of aortic valve interstitial cells during calcification. METHODS To determine the role of miRNA-30b in calcific aortic valve disease, we evaluated miRNA expression in human calcific aortic valve leaflets obtained intraoperatively. Furthermore, human valve interstitial cells were evaluated with regard to miRNA-30b expression and osteogenesis by quantitative real-time polymerase chain reaction, Western blotting, flow cytometry, and alkaline phosphatase assays. RESULTS In this study, we demonstrated that miRNA-30b attenuates bone morphogenetic protein 2-induced osteoblast differentiation by targeting Runx2, Smad1, and caspase-3. Transfection of a mimic of miRNA-30b led to decreases in alkaline phosphatase activity and expressions of Runx2, Smad1, and caspase-3. Furthermore, dual luciferase reporter assays confirmed that Runx2, Smad1, and caspase-3 are direct targets of miRNA-30b. CONCLUSIONS We demonstrated a remarkable role of miRNA-30b in calcific aortic valve disease as a regulator of human aortic valvular calcification and apoptosis through direct targeting of Runx2, Smad1, and caspase-3. Targeting of miRNA-30b could serve as a novel therapeutic strategy to limit progressive calcification in aortic stenosis.

Impact of preoperative atrial fibrillation on mortality and cardiovascular outcomes of mechanical mitral valve replacement for rheumatic mitral valve disease

OBJECTIVES The prognostic significance of preoperative atrial fibrillation on mitral valve replacement remains unclear. The aim of this study was to explore the effects of the presence of preoperative atrial fibrillation on mortality and cardiovascular outcomes of mitral valve replacement for rheumatic valve disease. METHODS A retrospective analysis was performed on a total of 793 patients who underwent mitral valve replacement with or without tricuspid valve repair in our hospital. The patients selected were divided into two groups according to preoperative rhythm status. Patients with preoperative atrial fibrillation were assigned to the AF group, while patients in preoperative sinus rhythm were assigned to the SR group. Postoperative follow-up was performed by outpatient visits, as well as by telephone and written correspondence. Data gathered included survivorship, postoperative complications, left ventricular function and tricuspid regurgitation. RESULTS For patients with atrial fibrillation vs those in sinus rhythm, there was no difference in postoperative mortality and morbidity. Follow-up was a mean of 8.6 ± 2.4 years. For patients with preoperative atrial fibrillation, 10-year survival from a Kaplan-Meier curve was 88.7%, compared with 96.6% in patients with preoperative sinus rhythm (P = 0.002). Multivariate analysis identified low left ventricular ejection fraction, older age, large left atrium and preoperative atrial fibrillation as significant adverse predictors for overall survival. Freedom from thromboembolism complications at 13 years was lower for patients with preoperative atrial fibrillation without maze procedure and left atrial appendage ligation, compared with that for patients with preoperative sinus rhythm without maze procedure and left atrial appendage ligation, and patients with concomitant maze procedure and left atrial appendage ligation (76.3 vs 94.8 vs 94.0%, respectively; P = 0.001). On echocardiography, the proportion of patients with significant tricuspid regurgitation was 38.7% (atrial fibrillation patients) vs 25.4% (patients in sinus rhythm; P < 0.001). Left ventricular ejection fraction measured 5 years after surgery increased by an average of 1.2% in the AF group, while it increased by 5.3% in the SR group (P = 0.028). CONCLUSIONS Preoperative atrial fibrillation is a risk factor for long-term mortality, thromboembolism complications and tricuspid regurgitation, and it also has an adverse effect on the degree of improvement when considering left ventricular function.

Meta-analysis of RAGE gene polymorphism and coronary heart disease risk.

Background Recent data from human and animal studies have shown an upregulated expression of advanced glycosylation end product–specific receptor (RAGE) in human atherosclerotic plaques 1 and in retina, messangial, and aortic vessels, suggesting an important role of RAGE in the pathogenesis of atherothrombotic diseases. In the past few years, the relationship between RAGE polymorphisms (−429T/C, −374T/A, and G82S) and coronary heart disease (CHD) has been reported in various ethnic groups; however, these studies have yielded contradictory results. Methods PubMed, ISI web of science, EMBASE and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. Data were abstracted independently by two reviewers. A meta-analysis was performed to examine the association between RAGE polymorphisms and susceptibility to CHD. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Results A total of 17 studies including 4343 patients and 5402 controls were involved in this meta-analysis. Overall, no significant results were observed for −429T/C (OR  = 1.01, 95% CI: 0.92–1.12, P  = 0.78), −374T/A (OR  = 1.11, 95% CI: 0.98–1.26, P  = 0.09) and G82S (OR  = 1.12, 95% CI: 0.86–1.45, P  = 0.41) polymorphism. In the stratified analyses according to ethnicity, sample size, CHD endpoint and Hardy-Weinberg status, no evidence of any gene-disease association was obtained. Conclusions This meta-analysis demonstrates that there is no association between the RAGE −429T/C, −374T/A and G82S polymorphisms and CHD.

Cardiac papillary fibroelastoma: a retrospect of four cases

ObjectiveWe have reviewed the medical histories of 4 patients who underwent operations between November 2004 and February 2011 at Changhai Hospital for cardiac papillary fibroelastoma.MethodsDiagnosis was demonstrably suggested by echocardiography. Tumor locations were mitral valve (1), left atrium (1), and aortic valve (2). Indications for operation were previous cerebrovascular accident for the mitral tumor, incidental apopsychia and giant mobile mass for the left atrium, ingravescent chest tightness and palpitations for the first aortic tumor, and severe regurgitation of aortic valve for the second aortic tumor. The study was approved by the Changhai Hospital Ethics Committee, and the consent from the patients or their immediate family was obtained.ResultsSurgical excision with necessary valve replacement operations was performed in all cases. All patients had uneventful postoperative recoveries. No evidence of regurgitation or recurrence was seen on echocardiography at follow-up.ConclusionsDespite their histologically benign aspect, cardiac papillary fibroelastomas should be removed because of potential embolic complications.

Aortic valve replacement with autologous pericardium: long-term follow-up of 15 patients and in vivo histopathological changes of autologous pericardium

OBJECTIVES The study aimed to assess the long-term follow-up of patients with an autologous pericardial aortic valve (APAV) replacement and to analyse in vivo histopathological changes in implanted APAVs. METHODS From 1996 to 1997, 15 patients (mean age, 34 years) underwent aortic valve replacement with the glutaraldehyde-treated autologous pericardium. All patients were followed up after discharge. The excised APAVs were processed for haematoxylin-eosin, Victoria blue-van Gieson and immunohistochemical staining. RESULTS The mean clinical follow-up was 11.43 ± 4.50 years. APAV-related in-hospital and late mortalities were both 0%. Five (33%) patients required reoperation because of a prolapse of the right coronary cusp (n = 1), infective endocarditis (n = 1) or fibrocalcific degeneration (n = 3). Freedom from endocarditis, fibrocalcific degeneration and reoperation at the end of follow-up was 93, 80 and 67%, respectively. The remaining 10 patients were alive and well with a mean New York Heart Association class of 1.10 ± 0.32 and normally functioning aortic valves (peak pressure gradient: 7.70 ± 3.41 mmHg; mean pressure gradient: 1.79 ± 0.64 mmHg). Histopathology revealed that (i) a thin factor VIII-positive layer (endothelialization) was found on all non-endocarditis APAVs; (ii) pericardial cells in all APAVs were positive for α-smooth muscle actin (myofibroblast phenotype) and some cells in the fibrocalcific APAVs were positive for alkaline phosphatase (osteoblast phenotype) and (iii) an elastic band was found in 3 cases (in vivo >9 years). CONCLUSIONS APAV replacement is a procedure with a low mortality. APAVs adapt to new environmental demands by producing an elastic band and by endothelialization, whereas myofibroblast/osteoblast transdifferentiation seems to be responsible for the fibrocalcification of APAVs.

Valve Repair With Autologous Pericardium for Organic Lesions in Rheumatic Tricuspid Valve Disease

BACKGROUND Surgical repair of pathologic tricuspid valve disease often fails because of severe anatomic distortion of the valve apparatus, particularly in patients with rheumatic heart disease. This usually leads to tricuspid valve replacement despite the associated prosthesis-related complications. This study examines our experience of tricuspid valve repair with autologous pericardium for organic rheumatic tricuspid valve disease. METHODS From 1996 to 2007, 31 patients underwent repairs for rheumatic tricuspid valve disease characterized by retracted leaflets and inadequate leaflet area. The patients, aged 14 to 56 years, had a mean New York Heart Association (NYHA) class of 2.9 +/- 0.6. All patients presented with severe tricuspid regurgitation and coexisting left-sided heart valve disease. Glutaraldehyde-treated autologous pericardial patch was used to augment tricuspid valve leaflets. Other techniques were applied as needed, including commissurotomy, leaflet mobilization, annuloplasty, and prosthetic ring implantation. Concomitant operations included left-sided valve replacement in all, and left atrial thrombus removal in 3 patients. Follow-up duration was 4 to 126 months. RESULTS No deaths or late reoperations occurred. All patients demonstrated clinical improvements on follow-up. Echocardiographic studies before hospital discharge showed less than mild tricuspid regurgitation in all patients. The most recent echocardiographic follow-up showed no tricuspid regurgitation in 10 patients (32.3%), trivial regurgitation in 12 (38.7%), mild regurgitation in 8 (25.8%), and moderate regurgitation in 1 (3.2%). CONCLUSIONS In selected patients, organic rheumatic tricuspid valve disease can be treated with pericardial patch to augment the retracted leaflets in combination with other techniques. Follow-up reveals excellent tricuspid valve function.

Mechanisms of aortic dissection smooth muscle cell phenotype switch

Objective: To investigate the expression of Nanog homeobox (NANOG) in thoracic aortic dissection (TAD) and the role of NANOG in regulating human aortic vascular smooth muscle cells (VSMCs) phenotype switch. Methods: Aortic specimens were collected from 20 patients undergoing TAD and 10 controls. VSMCs were isolated by adherent cultivation approach. The expression of NANOG, osteopontin (OPN), and VSMCs phenotype markers were determined by quantitative real‐time polymerase chain reaction, Western blot, immunohistochemistry, and immunofluorescence. Cell counting, scratch wound‐healing assay, Transwell migration, and apoptosis assays were used for cell function assessment. Deoxyribonucleic acid–protein binding detection was performed by chromatin immunoprecipitation. Results: Our experiment results showed that NANOG and OPN were highly expressed in TAD aortic wall and VSMCs, both accompanying VSMCs phenotype switch. Overexpression of NANOG induced the up‐regulation of VSMCs synthetic marker matrix metalloproteinase 2 and the down‐regulation of VSMCs contractile markers &agr;‐smooth muscle actin and smooth muscle 22&agr;. Overexpression of NANOG also enhanced the proliferation, migration, and antiapoptosis capabilities of VSMCs. The results also showed that these functions of NANOG was via OPN and NANOG directly up‐regulated OPN by binding to its promoter region. Conclusions: Our study suggests that NANOG is highly expressed in TAD aortic wall and VSMCs. Increased NANOG promotes VSMCs phenotype switch by directly up‐regulating OPN through binding to its promoter region.

Long-term results of modified sandwich repair of aortic root in 151 patients with acute type A aortic dissection

OBJECTIVES Acute type A aortic dissection frequently induces aortic root disease; however, the optimal surgical strategy for aortic root dissection remains a challenge. The objective of this study was to introduce a novel technique for reconstruction of type A dissection to improve patient prognosis. METHODS We performed a retrospective review of 791 consecutive patients with acute type A aortic dissection between January 2003 and July 2015. Among these patients, 151 were selected (72% men, age 51.7 ± 9.8 years) to have the modified sandwich repair of aortic root dissection. RESULTS The in-hospital mortality rate of the 151 patients was 6.6% (10/151). During a mean follow-up period of 52.7 ± 28.6 months, the survival rate was 100, 89.1 and 69.7% at 1, 5 and 10 years, respectively. Echocardiography and computed tomographic angiography were performed every year to monitor the pathological change in the aortic root. Freedom from severe aortic regurgitation at 5 years was 100%. No patients required reintervention due to dissection or pseudoaneurysm of the proximal aortic root. CONCLUSIONS Aortic valve resuspension and repair of the sinus of Valsalva with the modified sandwich technique using Teflon felt strips for acute type A dissection could be reliable and effective.

Retrograde Type A Dissection after Thoracic Endovascular Aortic Repair: Surgical Strategy and Literature Review

BACKGROUND In this study, we investigated the surgical strategy for managing retrograde type A dissection (RTAD) after thoracic endovascular aortic repair (TEVAR) by reporting our experience and literature review. METHODS From June 2011 to January 2014, nine patients with RTAD received surgical repair in our institution. The mean age of these patients was 49.3±10.7 years. Data on these RTAD patients was retrospectively collected for further analysis. Literature related to RTAD after TEVAR from 2006 to 2014 was reviewed using the following terms: thoracic endovascular aortic repair, retrograde type A dissection, stent induced new entry, and surgical repair. RESULTS We adopted a total arch replacement combined with a stented elephant trunk implantation and partly preserved the previous TEVAR stent during operation. In-hospital death rate was 11.1% (one of nine). One patient (11.1%) developed paraparesis after operation. No late deaths or complications occurred during follow-up. Literature review identified four articles on the surgical management of RTAD after TEVAR. Our literature review also showed total arch replacement with the stented elephant trunk implantation might be associated with a better prognosis. CONCLUSIONS Retrograde type A dissection is a serious complication after TEVAR. The induced factors of RTAD were various and complicated. Our experience and literature review indicates a combination of total arch replacement, stented elephant trunk implantation and partly preserving the previous TEVAR stent is feasible for the surgical repair of RTAD after TEVAR.