Update on surgical repair in functional mitral regurgitation.

BACKGROUND: Functional mitral regurgitation (FMR) is common in patients with myocardial infarction or dilated cardiomyopathy, and portends a poor prognosis despite guideline-directed medical therapy (GDMT). Surgical or transcatheter mitral repair for FMR from recent randomized clinical trials showed disappointing or conflicting results. AIMS: To provide an update on the role of surgical repair in the management of FMR. MATERIALS AND METHODS: A literature search was conducted utilizing PubMed, Ovid, Web of Science, Embase, and Cochrane Library. The search terms included secondary/FMR, ischemic mitral regurgitation, mitral repair, mitral replacement, mitral annuloplasty, transcatheter mitral repair, and percutaneous mitral repair. Randomized clinical trials over the past decade were the particular focus of the current review. RESULTS: Recent data underlined the complexity and poor prognosis of FMR. GDMT and cardiac resynchronization, when indicated, should always be applied. Accurate assessment of the interplay between ventricular geometry and mitral valve function is essential to differentiate proportionate FMR from the disproportionate subgroup, which could be helpful in selecting appropriate transcatheter intervention strategies. Surgical repair, most commonly performed with an undersized ring annuloplasty, remains controversial. Adjunctive valvular or subvalvular repair techniques are evolving and may produce improved results in selected FMR patients. CONCLUSION: FMR resulted from complex valve-ventricular interaction and remodeling. Distinguishing proportionate FMR from disproportionate FMR is important in exploring their underlying mechanisms and to guide medical treatment with surgical or transcatheter interventions. Further studies are warranted to confirm the clinical benefit of appropriate surgical repair in selected FMR patients.

MicroRNA-26b relieves inflammatory response and myocardial remodeling of mice with myocardial infarction by suppression of MAPK pathway through binding to PTGS2.

BACKGROUND: Myocardial infarction (MI) is a common cardiovascular disease caused by myocardial ischemia. Also, microRNA (miRNA) participates in the pathophysiology of many cardiovascular diseases, which can affect stem cell transplantation in the treatment of MI. In this study, our aim is to explore effect of miR-26b on inflammatory response and myocardial remodeling through the MAPK pathway by targeting PTGS2 in mice with MI. METHODS: Microarray data analysis was conducted to screen MI-related differentially expressed gens (DEGs). Relationship between miR-26b and PTGS2 was testified. Cardiac function, inflammatory reaction, infarct size, and myocardial fibrosis were observed. The miR-26b expression and mRNA and protein levels of, PTGS2, ERK, JNK and p38 and Bcl-2/Bax were examined. The effect of miR-26b on cell apoptosis was also analyzed. RESULTS: MiR-26b was predicted to target PTGS2 further to mediate the MAPK pathway, thus affecting MI. MiR-26b negatively targeted PTGS2. MI mice showed decreased cardiac function, as well as increased inflammatory reaction, myocardial injury, area of fibrosis and myocardial cell apoptosis. After injection of miR-26b agomir or NS-398 (PTGS2 inhibitor), inflammatory response of MI mice was attenuated and myocardial remodeling induced by MI was alleviated. CONCLUSION: These findings indicate that miR-26b inhibits PTGS2 to activate the MAPK pathway, so as to reduce inflammatory response and improve myocardial remodeling in mice with MI.

IRAK3 gene silencing prevents cardiac rupture and ventricular remodeling through negative regulation of the NF-κB signaling pathway in a mouse model of acute myocardial infarction.

Cardiac rupture and ventricular remodeling are recognized as the severe complications and major risk factors of acute myocardial infarction (AMI). This study aims to evaluate the regulatory roles of interleukin-1 receptor-associated kinase 3 (IRAK3) and nuclear factor-κB (NF-κB) signaling pathway in cardiac rupture and ventricular remodeling. Microarray analysis was performed to screen AMI-related differentially expressed genes and IRAK3 was identified. The models of AMI were established in male C57BL/6 mice to investigate the functional role of IRAK3. Afterwards, lentivirus recombinant plasmid si-IRAK3 was constructed for IRAK3 silencing. Next, cardiac function parameters were measured in response to IRAK3 silencing. The regulatory effects that IRAK3 had on myocardial infarct size and the content of myocardial interstitial collagen were analyzed. The regulation of IRAK3 silencing on the NF-κB signaling pathway was further assayed. The obtained results indicated that highly expressed IRAK3 and activated NF-κB signaling pathway were observed in myocardial tissues of mouse models of AMI, accompanied by increased expression of matrix metalloproteinase (MMP)-2/9 and tissue inhibitor of metalloproteinase 2 (TIMP-2). Notably, IRAK3 gene silencing inhibited the activation of NF-κB signaling pathway. Furthermore, IRAK3 gene silencing led to the decreased thickness of infarct area and collagen content of myocardial interstitium, alleviated diastolic, and systolic dysfunctions, as well as, facilitated cardiac functions in mice with AMI, corresponding to decreased expression of MMP-2/9 expression and increased expression of TIMP-2. Taken together, silencing of IRAK3 inactivates the NF-κB signaling pathway, and thereby impeding the cardiac rupture and ventricular remodeling, which eventually prevents AMI progression.

Quality Measurement and Improvement Study of Surgical Coronary Revascularization: Medication Adherence (MISSION-2).

BACKGROUND: Secondary preventive therapies play a key role in the prevention of adverse outcomes after coronary artery bypass grafting (CABG). However, medication adherence after CABG is often poor, and conventional interventions for improving adherence have limited success. With increasing penetration of smartphones, health-related smartphone applications might provide an opportunity to improve adherence. Carefully designed trials are needed to provide reliable evidence for the use of these applications in patients after CABG. METHODS: The Measurement and Improvement Studies of Surgical Coronary Revascularization: Medication Adherence (MISSION-2) study is a multicenter randomized controlled trial, aiming to randomize 1000 CABG patients to the intervention or control groups in a 1:1 ratio. We developed the multifaceted, patient-centered, smartphone-based Heart Health Application to encourage medication adherence in the intervention group through a health self-management program initiated during hospital admission for CABG. The application integrated daily scheduled reminders to take the discharge medications, cardiac educational materials, a dynamic dashboard to review cardiovascular risk factors and secondary prevention targets, and weekly questionnaires with interactive feedback. The primary outcome was secondary preventive medication adherence measured by the Chinese version of the 8-item Morisky Medication Adherence Scale at 6 months after randomization. Secondary outcomes included all-cause death, cardiovascular rehospitalization, and a composite of death, myocardial infarction, stroke, and repeat revascularization. DISCUSSION: Findings will not only provide evidence regarding the feasibility and effectiveness of the described intervention for improving adherence to CABG secondary preventive therapies but also explore a model for outpatient health self-management that could be translated to various chronic diseases and widely disseminated across resource-limited settings. TRIAL REGISTRATION: https://clinicaltrials.gov (NCT02432469).

The Effects of Phellinus linteus Polysaccharide Extracts on Cholesterol Efflux in Oxidized Low-Density Lipoprotein-Loaded THP-1 Macrophages.

The removal of excess cellular cholesterol is critical for maintaining cellular cholesterol homeostasis. Phellinus linteus polysaccharide extracts (PLPEs) is an immunomudulatory agent with a molecular weight of 153 kd. Here, we analyzed the effects of PLPEs on cholesterol efflux in oxidized low-density lipoprotein (ox-LDL)-loaded THP-1 (human acute monocytic leukemia cell line) macrophages. Various concentrations of PLPEs (5, 10, 20, and 100 µg/mL) were used to treat cells. Cholesterol efflux analysis was performed to analyze the cholesterol efflux ratio in PLPE-treated cells. Semiquantitative reverse transcription-polymerase chain reaction and Western blot analysis were conducted to assess the expression of target genes. Low dose of PLPEs (5-20 µg/mL) dose dependently enhanced cholesterol efflux to apolipoprotein A-I (ApoA-I), evidenced by promoting the expression of adenosine 5'-triphosphate (ATP)-binding cassette A1, ATP-binding cassette G1, and peroxisome proliferation-activated receptor γ, key regulators for cholesterol efflux. Moreover, GW9662, a potent antagonist of peroxisome proliferation-activated receptor γ, inhibited PLPE (20 µg/mL)-promoted cholesterol efflux to ApoA-I in a dose-dependent fashion. However, high dose of PLPEs (100 µg/mL) inhibited cholesterol efflux to ApoA-I from ox-LDL-loaded THP-1 macrophages, enhanced the production of superoxide anion, decreased mitochondrial membrane potential and ATP levels, and raised nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate oxidase subunits. Thus, these results indicate that low and high doses of PLPEs exhibit opposite effects on cholesterol efflux from ox-LDL-loaded THP-1 cells.

[Effects of on-pump beating-heart coronary artery bypass grafting for left-main patients].

OBJECTIVE: To explore the value of on-pump beating-heart coronary artery bypass grafting (OnP-BH CABG) for left-main patients with coronary heart disease through a comparative study with conventional coronary artery bypass grafting (CCABG). METHODS: The clinical data were retrospectively analyzed for 66 patients of OnP-BH and 48 control cases undergoing CCABG from January 2009 to January 2012 at Department of Cardiac Surgery, People's Hospital of Zhengzhou University. RESULTS: OnP-BH group had a better clinical outcome than CCABG group. There were obvious statistical difference in cardiopulmonary bypass (CPB) time, mean ventilation time, intensive care unit stay and recovery time of plasma cardiac troponin I (OnP-BH group vs CCABG group:(89 ± 25) vs (117 ± 28) min, (15 ± 14) vs (27 ± 19) h, (57 ± 27) vs (79 ± 34) h, (6.2 ± 1.8) vs (7.0 ± 2.4) d, all P < 0.05). The data of preoperative cTnI showed no significant difference between two groups (P > 0.05) .However, after CPB, significant intergroup difference existed in the level of cTnI (µg/L) OnP-BH group vs CCABG group: (0.5 h after CPB: (0.132 ± 0.022) vs (0.265 ± 0.014) , 1 h after CPB: (0.341 ± 0.027) vs (0.572 ± 0.046) , 1 h after operation: (0.641 ± 0.036) vs (0.932 ± 0.047) , 6 h after operation: (1.212 ± 0.765) vs (1.627 ± 0.542) and 24 h after operation: (1.496 ± 0.263) vs (1.734 ± 0.328) , all P < 0.05). CONCLUSIONS: On-pump beating-heart coronary artery bypass grafting is a feasible surgical approach for left-main patients. And it has a low risk and causes less myocardial damage.