Analysis of Genes Involved in Persistent Atrial Fibrillation: Comparisons of 'Trigger' and 'Substrate' Differences.

BACKGROUND/AIMS: Recent research has improved our understanding of the pulmonary vein and surrounding left atrial (LA-PV) junction and the left atrial appendage (LAA), which are considered the 'trigger' and 'substrate' in the development of atrial fibrillation (AF), respectively. Herein, with the aim of identifying the underlying potential genetic mechanisms, we compared differences in gene expression between LA-PV junction and LAA specimens via bioinformatic analysis. METHODS: Microarray data of AF (GSE41177) were downloaded from the Gene Expression Omnibus database. In addition, linear models for microarray data limma powers differential expression analyses and weighted correlation network analysis (WGCNA) were applied. RESULTS: From the differential expression analyses, 152 differentially expressed genes and hub genes, including LEP, FOS, EDN1, NMU, CALB2, TAC1, and PPBP, were identified. Our analysis revealed that the maps of extracellular matrix (ECM)-receptor interactions, PI3K-Akt and Wnt signaling pathways, and ventricular cardiac muscle tissue morphogenesis were significantly enriched. In addition, the WGCNA results showed high correlations between genes and related genetic clusters to external clinical characteristics. Maps of the ECM-receptor interactions, chemokine signaling pathways, and the cell cycle were significantly enriched in the genes of corresponding modules and closely associated with AF duration, left atrial diameter, and left ventricular ejection function, respectively. Similarly, mapping of the TNF signaling pathway indicated significant association with genetic traits of ischemic heart disease, hypertension, and diabetes comorbidity. CONCLUSIONS: The ECM-receptor interaction as a possible central node of comparison between LA-PV and LAA samples reflected the special functional roles of 'triggers' and 'substrates' and may be closely associated with AF duration. Furthermore, LEP, FOS, EDN1, NMU, CALB2, TAC1, and PPBP genes may be implicated in the occurrence and maintenance of AF through their interactions with each other.

Efficacy of Statin Therapy Related to Baseline Renal Function in Patients with Rheumatic Heart Disease Undergoing Cardiac Surgery.

BACKGROUND: Renal impairment increases the risk of cardiovascular events and perioperative complications in patients with heart valve disease. This study aimed to determine the perioperative benefit of statin treatment related to baseline renal function in patients with rheumatic heart disease (RHD) who had cardiac surgery. METHODS AND RESULTS: We performed a retrospective study on 136 patients with RHD who underwent valve replacement surgery. The mean age of the patients was 56.2 years, 59.6% were female, 8.8% patients had diabetes mellitus, and 27.2% of patients had hypertension. Overall, 3 patients died, 2 underwent reoperation, and 25 underwent thoracentesis during the study period. For patients with renal impairment, there was a higher risk of thoracic puncture (odds ratio [OR]: 3.33; 95% confidence interval [CI]: 1.36, 8.11; P < 0.01) and a longer time of drainage (difference in means: 1; 95% CI: 0.88, 1.12; P < 0.01), intensive care unit (ICU) stay (difference in means: 0.2; 95% CI: 0.17, 0.23; P = 0.02), and hospital stay (difference in means: 6.6; 95% CI: 6.15, 7.05; P < 0.01) compared with normal renal function. Furthermore, statins were associated with a reduction in drainage time (difference in means: -1.50; 95% CI: -1.86, -1.14; P = 0.02), ICU stay (difference in means: -0.30; 95% CI: -0.40, -0.20; P = 0.05), and hospital stay (difference in means: -5.40; 95% CI: -6.57, -4.23; P < 0.01) in patients with renal impairment (interaction, P ≤ 0.05 for all), but not in those with normal renal function. CONCLUSION: Statins have a greater clinical benefit in perioperative cardiac surgery with renal impairment. Statins are associated with a comparatively lower risk of thoracic puncture, as well as a reduced trend toward a reduction in drainage time, ICU stay, and hospital stay.

Biatrial versus Isolated Left Atrial Ablation in Atrial Fibrillation: A Systematic Review and Meta-Analysis.

OBJECTIVE: The outcomes of biatrial ablation (BA) and isolated left atrial ablation (LA) in atrial fibrillation remain inconclusive. In this meta-analysis, we assess the currently available evidence to compare outcomes between BA and LA. METHODS: Electronic searches were performed from database inception to December 2016, and relevant studies were accessed. Odds ratios and weight mean differences with 95% confidence intervals are reported. Twenty-one studies comprising 3609 patients were included in the present meta-analysis. RESULTS: The prevalence of sinus rhythm in the BA cohort was similar to that in the LA cohort at discharge, at 12 months, and after more than 1 year of follow-up. However, at 6 months, the prevalence of sinus rhythm was higher in the BA cohort than in the LA cohort. The rate of permanent pacemaker implantation was higher in the BA cohort than in the LA cohort. However, 30-day and late mortality and neurological events were similar between the BA and LA groups. CONCLUSION: There was no significant difference in the rate of restored sinus rhythm, the risk of death, and cerebrovascular events between BA and LA, but BA had a higher rate of permanent pacemaker implantation.

Safety and efficacy of the perioperative administration of recombinant human brain natriuretic peptide (rhBNP): a systematic review and meta-analysis.

OBJECTIVE: Retrospective studies and a meta-analysis were performed to evaluate the safety and effectiveness of the perioperative administration of recombinant human brain natriuretic peptide (rhBNP) during cardiac surgery under extracorporeal circulation. METHODS: Computerized literature searches were performed in Medline, Embase, The Cochrane Library, CNKI, CBM, and WANFANG to find randomized controlled trials (RCTs) related to the perioperative administration of rhBNP during cardiac surgery starting from the database inception until December 2016. Two researchers independently performed study screening, information extraction, and quality evaluation according to the inclusion/exclusion criteria, and a meta-analysis was performed using RevMan 5.2 software. RESULTS: A total of 12 studies were analyzed, including 12 RCTs and 727 patients. The meta-analysis results indicated that the perioperative administration of rhBNP could reduce the occurrence rate of postoperative complications, length of intensive care unit (ICU) stay, length of hospital stay, and serum creatinine (Scr) levels, and increase the 24-hour urine volume; however, it did not affect the postoperative mortality rate. CONCLUSION: The perioperative administration of rhBNP during cardiac surgery was safe and effective, and could improve the prognosis of the patients.

SIRT5 and post-translational protein modifications: A potential therapeutic target for myocardial ischemia-reperfusion injury with regard to mitochondrial dynamics and oxidative metabolism.

SIRT5 is a sirtuin family member that participates in dynamic and reversible protein chemical modification after translation. It has pivotal roles in the regulation of numerous aspects of myocardial energy metabolism and cardiac functions. Recent studies suggest that down-regulation of this regulator significantly increased the extent of myocardial infarction during ischemia-reperfusion injury (IRI). Accordingly, SIRT5 is emerging as a major contributor to the pathogenesis of IRI and may possess therapeutic potential for reversing mitochondrial respiratory chain disturbances and cellular damage attributed to ischemia-reperfusion. To better understand this specific mechanism, we reviewed the structure of SIRT5, its gene distribution and the SIRT5 pathways that influence myocardial IRI associated with mitochondrial dynamics and oxidative phosphorylation.

Efficacy and Mechanism of Preoperative Simvastatin Therapy on Myocardial Protection after Extracorporeal Circulation.

BACKGROUND: Cardiopulmonary bypass (CPB) causes systemic inflammatory response and ischemia-reperfusion (IR) injury. OBJECTIVE: To investigate the effect and mechanism of simvastatin on myocardial injury in cardiac valve surgery with CPB. METHODS: One hundred thirty patients were randomly assigned to the statin group (n = 65) or control group (n = 65). Simvastatin was administered preoperatively and postoperatively. Duration of intensive care unit stay, duration of assisted ventilation, and left ventricular ejection fraction were recorded. Plasma was analysed for troponin T (cTnT), isoenzyme of creatine kinase (CK-MB), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8). Ultrastructure of the myocardium and autophagosomes were observed. Beclin-1, LC3-II/I, P62, AMPK, and the phosphorylation of AMPK in cardiomyocytes were detected. RESULTS: Simvastatin significantly reduced the duration of assisted ventilation (P = 0.030) and ejection fraction was significantly higher in the statin group (P = 0.024). Simvastatin significantly reduced the levels of cTnT, CK-MB, TNF-α, IL-6, and IL-8 (P < 0.05), reduced the expression of LC3-II/LC3-I and Beclin 1, and increased the expression of phosphorylation of AMPK. Simvastatin reduced the generation of autophagosomes and the ultrastructural injuries to myocardium. CONCLUSION: Perioperative statin therapy reduced myocardial injury by regulating myocardial autophagy and activating the phosphorylation of AMPK. The registration number of this study is ChiCTR-TRC-14005164.

Meta-analysis of safety and efficacy for direct oral anticoagulation treatment of non-valvular atrial fibrillation in relation to renal function.

INTRODUCTION: We performed a meta-analysis of the safety and efficacy of anticoagulation treatment for atrial fibrillation (AF) in relation to renal function. We also examined the change in estimated glomerular filtration rate (eGFR) from baseline and compared the outcomes for patients with stable and worsening renal function. MATERIALS AND METHODS: We selected studies that used randomized controlled trials in which outcomes for direct oral anticoagulants (DOACs) (dabigatran, rivaroxaban, apixaban, or edoxaban) were compared with those for warfarin in AF patients with normal, mild or moderate renal function, except the severe one (creatinine clearance<30). RESULTS: We assessed five clinical trials, involving 72,608 patients. Pooled analysis indicated that the risk of stroke was lower for DOACs than for warfarin among patients with mild renal impairment (Risk ratio, 0.79; 95% confidence interval, 0.68-0.91) and moderate renal impairment (0.80, 0.69-0.92). No major differences were found in patients with normal renal function. Additionally, DOACs were associated with fewer major bleeds among patients with normal (0.77, 0.70-0.84), mild (0.86, 0.77-0.95), and moderate renal impairment (0.73, 0.65-0.82). Among those treated with DOACs, a lower dosage was associated with lower risk of major bleeding (0.75, 0.68-0.83) and higher risk of stroke or systemic embolism (1.28, 1.12-1.47). Further, DOACs tended to be associated with a lower estimated glomerular filtration rate (eGFR) than warfarin even after 30months. Finally, we found significant differences in the risk of stroke (2.09, 1.64-2.68) and major bleeding (2.01, 1.66-2.42) between patients with stable and worsening renal function. CONCLUSIONS: DOACs have a greater clinical benefit than warfarin with respect to renal function. They are associated with a comparatively lower risk of stroke and major bleeding, as well lower eGFR. This suggests these agents are a better choice in patients with renal disease.

Neurocardiology: Cardiovascular Changes and Specific Brain Region Infarcts.

There are complex and dynamic reflex control networks between the heart and the brain, including cardiac and intrathoracic ganglia, spinal cord, brainstem, and central nucleus. Recent literature based on animal model and clinical trials indicates a close link between cardiac function and nervous systems. It is noteworthy that the autonomic nervous-based therapeutics has shown great potential in the management of atrial fibrillation, ventricular arrhythmia, and myocardial remodeling. However, the potential mechanisms of postoperative brain injury and cardiovascular changes, particularly heart rate variability and the presence of arrhythmias, are not understood. In this chapter, we will describe mechanisms of brain damage undergoing cardiac surgery and focus on the interaction between cardiovascular changes and damage to specific brain regions.