Diagnostic value of circulating microRNA-19b in heart failure.

OBJECTIVE: For differentiating heart failure (HF) with preserved ejection fraction (HFpEF) from HF with reduced EF (HFrEF), N-terminal prohormone brain natriuretic peptide (NT-proBNP) is less accurate. Decreased expression of microRNA-19b (miR-19b) is associated with increased cardiac-fibrosis. We aim to evaluate the value of miR-19b in diagnosing HFrEF patients. METHOD: We included 200 HF patients and 100 healthy controls. Intergroup comparisons of miR-19b were made and correlation between miR-19b and NT-proBNP was analysed. Diagnostic values of NT-proBNP and miR-19b for HF patients versus controls and HFrEF versus HFpEF were obtained by ROC analysis and described by area under curve (AUC), sensitivity and specificity. RESULTS: HFrEF patients (0.87, 95% CI 0.37-1.45) had significantly lower miR-19b level than HFpEF group (1.32, 95% CI 0.63-2.51) and the controls (1.82, 95% CI 0.37-1.45) (both P < .001). There was a remarkable negative correlation between miR-19b and NT-proBNP (P < .001). The additional use of miR-19b did not improve the accuracy of NT-proBNP alone in diagnosing HF patients from the controls (both AUC = 0.98, 95%CI 0.97-0.99). However, as for distinguishing the HFpEF from HFrEF, miR-19b and NT-proBNP yielded a significantly higher AUC than NT-proBNP alone (0.85, 95% CI 0.80-0.90 vs. 0.66, 95% CI 0.58-0.74) (P < .001), and the sensitivity for diagnosing HFrEF was raised from 58% to 77% and the specificity from 75% to 79%. CONCLUSIONS: On top of NT-proBNP, miR-19b added the value in diagnosing HFrEF. But in view of satisfactory accuracy of NT-proBNP in predicting HF from the healthy volunteers, miR-19b did not provide incremental value.

Association of triglyceride glucose index and its combination of obesity indices with prehypertension in lean individuals: A cross-sectional study of Chinese adults.

For normal-weight population, the management of prehypertension may be more beneficial by identifying insulin resistance (IR) status than relying solely on traditional indicators of obesity. We investigated the association of triglyceride glucose (TyG) index, a simple surrogate marker of IR, and its combination of obesity indices with prehypertension in lean individuals. A total of 105 070 lean adults without hypertension were included in this analysis. Body mass index (BMI), waist circumference (WC), waist-to-height ratio (WtHR), and TyG were calculated according to the corresponding formula; TyG-BMI, TyG-WC, and TyG-WHtR were calculated by multiplying the corresponding two parameters. Gardner-Altman plots, partial correlation, and logistic regression analyses were applied to explore the associations in continuous variables and quartiles. The prehypertensive ones had higher mean values of TyG, TyG-BMI, TyG-WC, and TyG-WHtR than normotensive individuals. All the four indicators showed positive correlations with systolic blood pressure and diastolic blood pressure. After full adjustment, only TyG-BMI and TyG-WC were significantly associated with prehypertension in both genders. Furthermore, TyG-BMI had the highest OR for prehypertension. Our study showed that TyG-BMI might be an accessible and complementary monitor in the hierarchical management of non-obese prehypertensive patients.

Differential expression profile of long non-coding RNA in cardiomyocytes autophagy induced by angiotensin II.

Autophagy is a ubiquitous intracellular process for cellular homeostasis maintenance by recycling damaged protein and organelles. Dysregulation of cardiomyocytes autophagic activity is implicated in various heart diseases. Recent studies had demonstrated that long non-coding RNAs (lncRNAs) played crucial roles on modulation of autophagic activity. In this study, we first established an angiotensin II-induced autophagy model on neonatal rat cardiomyocytes. Western blot assay confirmed that the expression of Beclin 1 and the conversion of soluble LC3-I to lipid bound LC3-II were significantly increased at 12 h after angiotensin II stimulation, but the cardiomyocytes surface area and hypertrophic markers expression had no significant change. Then microarray analysis and real-time PCR were applied to detect differentially expressed lncRNAs during cardiomyocytes autophagy. A total of 1,249 lncRNAs were determined as differentially expressed, including 700 upregulated lncRNAs and 549 downregulated lncRNAs. LncRNAs subgroup analysis showed there were 43 transcribed ultra-conserved noncoding RNAs (T-UCRs) differentially expressed in cardiomyocytes autophagy, of which 26 T-UCRs were upregulated and 17 T-UCRs were downregulated. Bioinformatics analysis further showed that 94 differentially expressed lncRNAs contained potential binding sites of miR-22, a pro-hypertrophic and pro-autophagic microRNA. Therefore, these differentially expressed lncRNAs might play critical roles in cardiomyocytes autophagy. This finding would provide an experimental basis for future investigation on ischemic heart disease.

Dynamic autophagic activity affected the development of thoracic aortic dissection by regulating functional properties of smooth muscle cells.

The aortic medial degeneration is the key histopathologic feature of Thoracic aortic dissection (TAD). The aim of this study was to identify the change of autophagic activity in the aortic wall during TAD development, and to explore the roles of autophagy on regulating functional properties of smooth muscle cells (SMCs). Firstly, compared with control group (n = 11), the increased expression of autophagic markers Beclin1 and LC3 was detected in the aortic wall from TAD group (n = 23) by immunochemistry and western blot. We found that more autophagic vacuoles were present in the aortic wall of TAD patients using Transmission electron microscopy. Next, autophagic activity was examined in AD mice model established by ß-aminopropionitrile fumarate (BAPN) and angiotensin II. Immunochemistry proved that autophagic activity was dynamically changed during AD development. Beclin1 and LC3 were detected up-regulated in the aortic wall in the second week after BAPN feeding, earlier than the fragmentation or loss of elastic fibers. When AD occurred in the 4th week, the expression of Beclin1 and LC3 began to decrease, but still higher than the control. Furthermore, autophagy was found to inhibit starvation-induced apoptosis of SMCs. Meanwhile, blockage of autophagy could suppress PDGF-induced phenotypic switch of SMCs. Taken together, autophagic activity was dynamically changed in the aortic wall during TAD development. The abnormal autophagy could regulate the functional properties of aortic SMCs, which might be the potential pathogenesis of TAD.

Inhibition of heat shock protein 90 improves pulmonary arteriole remodeling in pulmonary arterial hypertension.

While the molecular chaperone heat shock protein 90 (HSP90) is involved in a multitude of physiological and pathological processes, its role relating to pulmonary arterial hypertension (PAH) remains unclear. In the present study, we investigated the effect in which HSP90 improves pulmonary arteriole remodeling, and explored the therapeutic utility of targeting HSP90 as therapeutic drug for PAH. By Elisa and immunohistochemistry, HSP90 was found to be increased in both plasma and membrane walls of pulmonary arterioles from PAH patients. Moreover, plasma HSP90 levels positively correlated with mean pulmonary arterial pressure and C-reactive protein. In a monocrotaline-induced rat model of PH, we found that 17-AAG, a HSP90-inhibitor, alleviated the progress of PH, demonstrated by lower pulmonary arterial pressure and absence of right ventricular hypertrophy. Immunohistochemical staining demonstrated that 17-AAG improved pulmonary arteriole remodeling on the basis of reduced wall thickness and wall area. The inflammatory response attributed to PH could be attenuated by 17-AAG through reduction of NF-κB signaling. Moreover, 17-AAG was found to suppress PDGF-stimulated proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) through induction of cell cycle arrest in the G1 phase. In conclusion, HSP90 inhibitor 17-AAG could improve pulmonary arteriole remodeling via inhibiting the excessive proliferation of PASMCs, and inhibition of HSP90 may represent a therapeutic avenue for the treatment of PAH.

Endothelial progenitor cells in ischemic stroke: an exploration from hypothesis to therapy.

As the population ages and lifestyles change in concordance, the number of patients suffering from ischemic stroke and its associated disabilities is increasing. Studies on determining the relationship between endothelial progenitor cells (EPCs) and ischemic stroke have become a new hot spot and have reported that EPCs may protect the brain against ischemic injury, promote neurovascular repair, and improve long-term neurobehavioral outcomes. More importantly, they introduce a new perspective for prognosis assessment and therapy of ischemic stroke. However, EPCs' origin, function, influence factors, injury repair mechanisms, and cell-based therapy strategies remain controversial. Particularly, research conducted to date has less clinical studies than pre-clinical experiments on animals. In this review, we summarized and analyzed the current understanding of basic characteristics, influence factors, functions, therapeutic strategies, and disadvantages of EPCs as well as the regulation of inflammatory factors involved in the function and survival of EPCs after ischemic stroke. Identifying potential therapeutic effects of EPCs in ischemic stroke will be a challenging but an incredibly important breakthrough in neurology, which may bring promise for patients with ischemic stroke.

Immediate- and medium-term effects of simultaneous percutaneous corrections of secundum type atrial septal defect combined with pulmonary valve stenosis in local anesthesia and without transesophageal echocardiography guidance.

BACKGROUND: The feasibility and efficacy of simultaneous percutaneous treatment of secundum type atrial septal defect (ASD) combined with pulmonary valve stenosis (PS) have not been proved. OBJECTIVE: To evaluate the safety and efficacy on the clinical benefit of simultaneous percutaneous correction of these two pathologies under local anesthesia and without transesophageal echocardiography guidance. METHODS: Transpulmonary gradient, functional status, pulmonary regurgitation (PR), and tricuspid regurgitation (TR) were studied in 35 patients undergoing percutaneous balloon pulmonary valvuloplasty and ASD closure from March 2004 to July 2012. All patients were followed up until January 2013, an average of 39 months. RESULTS: According to color Doppler transthoracic echocardiography (TTE) before the intervention, the ASD defect size and transpulmonary gradient were 17±8.4 mm and 88±37.8 mmHg, respectively. Post-interventionally, the peak-to-peak transpulmonary gradient decreased from 77±37.6 mmHg to 20±16.2 mmHg (p<0.001) and the ASD occluder size was 23±10.5 mm. In all those patients, there was no residual shunt detected, and moderate and severe TR decreased from 45.7% (16/35) and 20% (7/35) to 8.6% (3/35) and 5.7% (2/35) before and after intervention detected by TTE, respectively. Eight patients had mild PR after procedure and two of them recovered at 6 months and no patient encountered severe adverse events at the latest follow-up. CONCLUSION: Simultaneous percutaneous corrections of ASD combined with PS are feasible, safe, and effective with satisfactory results.

Decreased tricuspid regurgitation following percutaneous closure of congenital perimembranous ventricular septal defect: immediate and 6-month echocardiographic assessment.

As a common concomitant performance and the most frequent complications of transcatheter perimembranous ventricular septal defect (VSD) closure, tricuspid regurgitation (TR) has rarely been concerned. From January 2008 to December 2012, a total of 70 patients (men: 33, women: 37; mean age: 30.0 ± 17.1 years) with at least mild TR before VSD closure were examined in 508 consecutive congenital perimembranous VSD patients to investigate the outcomes of TR. After VSD closure, the jet area decreased from 3.4 ± 2.5 to 1.2 ± 2.5 cm(2) (p < 0.001); however, no significant decrease was found in 3 patients (mean age 59.7 ± 2.5 years) with severe TR (12.0 ± 1.2 versus 11.2 ± 3.2 cm(2), p = 0.668). Compared to the early outcome after VSD closure, the jet area detected by TTE at 6-month follow-up had further decreased (1.2 ± 2.5 versus 0.9 ± 2.2 cm(2), p < 0.001). In 6 patients, a slight residual shunt was detected immediately after VSD closure and diminished in 3 patients at 6-month follow-up. The hemolysis occurred in one of these six patients and recovered after 3 days. In conclusion, functional TR was ameliorated after percutaneous VSD closure, although persistent abundant TR was common in patients with severe TR before procedure.

Simultaneous transcatheter treatment of perimembranous ventricular septal defect and other congenital cardiopathies.

OBJECTIVE: To assess the efficacy and safety of simultaneous transcatheter corrections of perimembranous ventricular septal defect (VSD) and other congenital cardiopathies. PATIENTS/METHODS: From 2004 to 2012, 56 patients (25 male, 31 female), aged 14.2±10.1, with compound congenital cardiovascular abnormalities underwent simultaneous transcatheter interventional procedure. Of the 56 patients, 32 had VSD and atrial septal defects (ASD); 17 had VSD and patent ductus arteriosus (PDA); and seven had VSD and pulmonary valve stenosis (PS). Percutaneous balloon pulmonary valvuloplasty (PBPV) was performed before the closure of VSD, PDA, or ASD. RESULTS: The combined transcatheter interventional procedure was successfully performed in all patients. Among these, two occluders were implanted in each of 49 patients, seven patients with VSD combined with PS underwent successfully balloon valvuloplasty and VSD closure. The size of VSD, ASD and PDA detected by TTE was 4.8±1.7 mm, 9.0±5.0 mm and 4.5±2.5 mm, respectively. The occluder diameter of VSD, ASD and PDA was 7.6±2.2 mm, 14.3±6.2 mm and 7.9±3.2 mm, respectively. The peak-to-peak transpulmonary gradient decreased from 60.4±19.7 mmHg to 15.0±5.0 mmHg (p<0.001) in seven patients with VSD combined with PS. One patient with VSD and ASD had a permanent pacemaker implanted because of third-degree atrioventricular block two months after the procedure. There were not serious adverse events in relation to the combined procedures during the 23.8±20.7 months of follow-up in other 55 patients. CONCLUSION: The simultaneous treatment of VSD and other congenital cardiopathies using transcatheter-based procedures is safe and effective, which can provide satisfactory results.

Comparison of medium-term results of transcatheter correction versus surgical treatment for secundum type atrial septal defect combined with pulmonary valve stenosis.

This study was undertaken to compare the clinical results of traditional surgery and a percutaneous procedure for secundum type atrial septal defect (ASD) combined with pulmonary valve stenosis (PS). A total of 78 consecutive patients were identified between March 2004 and July 2012 in our institution. Thirty-five patients (44.9%) underwent percutaneous correction and the remaining 43 patients (55.1%) were treated surgically. All patients had simultaneous complete correction in both groups and no serious complications occurred. The surgical group was significantly younger (13.9 ± 13.0 versus 31.0 ± 17.5 years, P < 0.001) and had a longer mean hospital stay (12.6 ± 4.7 versus 5.3 ± 1.5 days, P < 0.001). There were no significant differences in defect size (18.0 ± 7.9 versus 16.9 ± 8.4 mm, P = 0.553) and transvalvular gradient detected by transthoracic echocardiography (TTE) (74.7 ± 28.3 versus 87.6 ± 37.8 mmHg, P = 0.089) between the two groups. Significant tricuspid regurgitation (TR) decreased from 66% to 14% in the transcatheter group and from 40% to 9% in the surgical group. Mild pulmonary regurgitation was detected in 8 patients in the transcatheter cohort and in 6 patients in the surgical cohort after the procedure. At last follow-up, 83% and 93% of the patients in the transcatheter and surgical groups, respectively, were free of any symptoms, and a significant improvement from preprocedure was observed in the transcatheter group but not in the surgical group (P = 0.005 and P = 0.062). In conclusion, transcatheter correction is a valuable alternative to surgery and allows more patients to be effectively treated in China.

Percutaneous closure of postinfarct muscular ventricular septal defects: a multicenter study in China.

BACKGROUND: Surgical repair is an effective method to treat ventricular septal defect (VSD) complicating acute myocardial infarction (AMI). However, the mortality rate remains high. This study was designed to assess the immediate and mid-term results of transcatheter closure of postinfarct muscular VSDs. METHODS: Data were retrospectively collected from 42 AMI patients who underwent attempted transcatheter VSD closure between 2008 and 2012 in seven heart centers of China. RESULTS: Nine patients underwent emergent VSD closure in the acute phase (within two weeks from VSD) while the others underwent elective closure. The time between VSD occurrence and closure in emergency group and elective group was 7.7 ± 2.3 days and 35 ± 14.5 days, respectively (p<0.01). The percentage of procedure success in the emergency group and elective group was 77.8% (7/9) and 97% (32/33), respectively (p=0.048). The hospital mortality was higher for emergent closure in comparison to elective closure (66.7% vs. 6.1%, p<0.01). During a median follow-up of 25 months (0-58 months), two patients died at 8 and 29 months, respectively, and no serious complications occurred in other patients. CONCLUSION: Interventional postinfarct VSD closure is a safe and effective approach that can be performed with a high procedural success rate, with favorable outcomes if it can be undertaken >14 days postinfarct.