PGC-1α, a potent transcriptional coactivator, is the major regulator of mitochondrial biogenesis and activity in the cardiac muscle. The dysregulation of PGC-1α and its target genes has been reported to be associated with congenital and acquired heart diseases. By examining myocardium samples from patients with Tetralogy of Fallot, we show here that PGC-1α expression levels are markedly increased in patients compared with healthy controls and positively correlated with the severity of cyanosis. Furthermore, hypoxia significantly induced the expression of PGC-1α and mitochondrial biogenesis in cultured cardiac myocytes. Mechanistic studies suggest that hypoxia-induced PGC-1α expression is regulated through the AMPK signaling pathway. Together, our data indicate that hypoxia can stimulate the expression of PGC-1α and mitochondrial biogenesis in the cardiac myocytes, and this process might provide a potential adaptive mechanism for cardiac myocytes to increase ATP output and minimize hypoxic damage to the heart.
Early and convenient diagnosis is urgently needed for acute Stanford type A aortic dissection (AAAD) patients due to its high mortality within the first 48 hours. Circulating microRNAs (miRNAs) are promising biomarkers of cardiovascular diseases, however, little is known about circulating miRNAs involved in AAAD. Here, the blood serum was sampled from 104 AAAD+ patients and 103 age-matched donors. Initial screening was conducted using the TaqMan Low Density Array followed by RT-qPCR confirmation. According to the two-phase selection and validation process, we found that miR-25, miR-29a and miR-155 were significantly elevated, while miR-26b was markedly decreased in AAAD+ serum samples compared with AAAD− individuals. Most importantly, for individuals with hypertension, which is a major contributor to AAAD, the 4-miRNA panel also showed high accuracy in predicting those who are more likely to develop AAAD. In the blind trial set, the panel correctly classified 93.33% AAAD+ patients and 86.67% controls from the hypertension cohort. Finally, the serum miRNA-based biomarker for early AAAD detection was supported by a retrospective analysis. Taken together, we identify a distinct profile of 4-miRNA that can serve as a noninvasive biomarker for AAAD diagnosis, especially for those with hypertension.
Transforming growth factor-β1 (TGF-β1) is an important mediator of atrial fibrosis and atrial fibrillation (AF). But the involved genetic mechanism is unknown. Herein, the TGF-β1 C-509T polymorphism (rs1800469) was genotyped in a case-control study of 840 patients and 845 controls in Chinese population to explore the association between the polymorphism and susceptibility and prognosis of lone AF. As a result, the CT and/or TT genotypes had an increased lone AF risk [adjusted odds ratio (OR) = 1.50 for CT, OR = 3.72 for TT, and OR = 2.15 for CT/TT], compared with the TGF-β1CC genotype. Moreover, patients carrying CT/TT genotypes showed a higher possibility of AF recurrence after catheter ablation, compared with patients carrying CC genotype. In a genotype-phenotype correlation analysis using 24 normal left atrial appendage samples, increasing gradients of atrial TGF-β1 expression levels positively correlated with atrial collagen volume fraction were identified in samples with CC, CT and TT genotypes. The in vitro luciferase assays also showed a higher luciferase activity of the -509T allele than that of the -509C allele. In conclusion, the TGF-β1 C-509T polymorphism is involved in the etiology of lone AF and thus may be a marker for genetic susceptibility to lone AF and predicting prognosis after catheter ablation in Chinese populations. Therefore, we provide new information about treatment strategies and our understanding of TGF-β1 in AF.
17 November 2017 in Interactive CardioVascular and Thoracic Surgery
The best surgical strategy for acute Stanford Type A aortic dissection (aTAAD) involving the arch remains controversial. Here, we report on the satisfactory results following aTAAD repair using a novel arch fenestrated stent graft. From December 2014 to December 2015, 42 aTAAD patients (27 male and 15 female) underwent ascending aorta replacement and fenestrated stent graft implantation. The fenestrated stent graft was implanted into the true lumen of the aortic arch and proximal descending aorta, with the fenestration opening located at the ostia of 3 head vessels in the arch. The proximal end of the stent graft was anastomosed to the distal end of the Dacron tube graft that replaced the proximal ascending aorta. All patients underwent contrast-enhanced computed tomography angiography prior to discharge and during follow-up. The average cardiopulmonary bypass duration was 213 ± 49 min, aortic cross-clamp duration was 133 ± 39 min and unilateral cerebral perfusion and lower body arrest duration was 27 ± 8 min. There were 2 in-hospital deaths due to circulation failure (mortality 4.8%). During a mean follow-up period of 7.4 ± 3.2 months, 1 patient with Behçet's disease died of aortic root pseudoaneurysm. The 39 surviving patients underwent contrast-enhanced computed tomography scans at 3, 6 and 12 months, which indicated increasing false-lumen thrombosis. In aTAAD patients, the use of the novel arch fenestrated stent graft achieved excellent aortic remodelling of the aortic arch and descending aorta without any increase in the morbidity and mortality.
Background: Deep sternal wound infection (DSWI) is a severe complication following cardiac surgery. A retrospective study was implemented to determine the risks and clinical characteristics of DSWI after cardiac operation in the Chinese population. Methods: We analysed 7,944 consecutive patients who underwent cardiac surgery via median sternotomy from January 2002 to December 2016 at our institution. Multiple logistic regression analysis was used to identify risk factors for DSWI. Results: A total of 106 patients (1.33%) suffered from DSWI; significant risk factors included body mass index (BMI) (P=0.02; OR=1.08; 95% CI: 1.01–1.16) and reoperation (P<0.01; OR=5.93; 95% CI: 2.88–12.25). The most common bacterium involved in DSWI was staphylococcus aureus (23%). Among all DSWI patients, the overall survival rate of the group treated with flap reconstruction was significantly higher than that in the group treated with intravenous antibiotics and sternal debridement (87% vs. 59%, P=0.01). Conclusions: DSWI was associated with several risk factors. Effective intervention strategies could improve the outcome of patients undergoing cardiac surgery.
21 September 2017 in Journal of Cardiothoracic Surgery
Reoperative cardiac valve surgery via sternotomy is associated with a substantial morbidity and mortality. This study evaluated the right anterolateral thoracotomy for high-risk patients undergoing mitral and tricuspid valve redo procedures. Out of a series of 173 patients undergoing redo cardiac valve surgery, 24 patients were reoperative via the right anterolateral thoracotomy as the high-risk group on the basis of the proximity of the heart and great vessels to the sternum and the presence and location of patent bypass grafts. In all cases, sternotomy was avoided. The mitral valve and tricuspid valve were replaced in 4 and 19 patients and repaired in 1 and 2 patients, respectively. Moreover, left atrial folding was performed in 5 patients. Mortality was 8.3%. All other patients had uneventful outcomes and normal valve function at follow-up. Reoperative cardiac valve surgery can be performed safely using the right anterolateral thoracotomy in high-risk patients. It offers enough exposure. It minimizes the need for cardiac dissection, and thus, the risk for injury. Avoiding a high-risk resternotomy increases patients comfort and safety of redo mitral and tricuspid valve surgery.