Mitral Loop Cerclage Annuloplasty for Secondary Mitral Regurgitation: First Human Results.

OBJECTIVES: This is an early feasibility clinical test of mitral loop cerclage annuloplasty to treat secondary mitral valve regurgitation. BACKGROUND: Secondary mitral regurgitation is characterized by cardiomyopathy, mitral annular enlargement, and leaflet traction contributing to malcoaptation. Transcatheter mitral loop cerclage applies circumferential compression to the mitral annulus by creating a loop through the coronary sinus across the interventricular septum, protecting entrapped coronary arteries from compression, and interactive annular reduction under echocardiographic guidance. This is the first human test of mitral loop annuloplasty. METHODS: Five subjects with severe symptomatic secondary mitral regurgitation underwent mitral loop cerclage, with echocardiographic and computed tomography follow-up over 6 months. RESULTS: Mitral loop cerclage was successful in 4 of 5 subjects and aborted in 1 of the 5 because of unsuitable septal coronary vein anatomy. Immediately and over 6 months, measures of both mitral valve regurgitation (effective orifice area and regurgitation fraction) and chamber dimensions (left atrial and left ventricular volumes) were reduced progressively and ejection fractions increased. Two with persistent and permanent atrial fibrillation spontaneously reverted to sinus rhythm during follow-up. One subject experienced a small myocardial infarction from an unrecognized small branch coronary occlusion. Another, experiencing cardiogenic shock at baseline, died of intractable heart failure after 6 weeks. CONCLUSIONS: In this first human test, mitral loop cerclage annuloplasty was successful in 4 of 5 attempts, caused reverse remodeling (reduction in secondary mitral regurgitation and heart chamber volumes), and suggested electrical remodeling (reversion of atrial fibrillation). Further evaluation is warranted.

Left ventricular end-diastolic dimension as a predictive factor of outcomes in children with acute myocarditis.

In this study, we sought predictors of mortality in children with acute myocarditis and of incomplete recovery in the survivor group. We classified our patients into three groups according to their outcomes at last follow-up: full recovery was classified as group I, incomplete recovery was classified as group II, and death was classified as group III. In total, 55 patients were enrolled in the study: 33 patients in group I, 11 patients in group II, and 11 patients in group III. The initial left ventricular fractional shortening - left ventricular fractional shortening - was significantly lower in group III (p=0.001), and the left ventricular end-diastolic dimension z score was higher in groups II and III compared with group I (p=0.000). A multivariate analysis showed that the left ventricular end-diastolic dimension z score (odds ratio (OR), 1.251; 95% confidence interval (CI), 1.004-1.559), extracorporeal membrane oxygenation (OR, 9.842; 95% CI, 1.044-92.764), and epinephrine infusion (OR, 18.552; 95% CI, 1.759-195.705) were significant predictors of mortality. The left ventricular end-diastolic dimension z score was the only factor that predicted incomplete recovery in the survivor group (OR, 1.360; 95% CI, 1.066-1.734; p=0.013). The receiver operating characteristic curve of the left ventricular end-diastolic dimension z score at admission showed a cut-off level of 3.01 for predicting mortality (95% CI, 0.714-0.948). In conclusion, a high left ventricular end-diastolic dimension z score on admission was a significant predictor of worse outcomes, both regarding mortality and incomplete recovery.

Mitral loop cerclage as a variant form of mitral cerclage annuloplasty that adds a device (CSTV) for preventing potential complications: a preclinical proof of concept and feasibility study.

AIMS: Although mitral cerclage annuloplasty can reduce mitral regurgitation, the potential risks for erosion of the surrounding tissue or conduction blockage are barriers to human translation. This preclinical study aimed to provide a proof of concept for a novel approach, mitral loop cerclage (MLC), designed to address these shortcomings. METHODS AND RESULTS: MLC consists of: (1) a novel appliance termed a coronary sinus and tricuspid valve protective device (CSTV) that includes a tension locker, and (2) a nylon-coated, braided stainless steel rope (0.6 mm thick) with a coronary artery protective device in a single unit (cerclage rope). Nine healthy farm swine underwent MLC in short-term (two weeks, n=4) and midterm (six weeks, n=5) survival experiments under X-ray fluoroscopic guidance imaging. The procedural success rate was 100%. MLC resulted in a significant reduction of the septal lateral dimension of the mitral annulus (24.58±2.16 vs. 21.26±1.43 mm, p=0.04) and left ventricular (LV) volume in diastole (75.9±3.9 vs. 70.6±5.0 ml, p=0.04) in the midterm group. No conduction abnormalities or serious complications were noted beyond trivial tricuspid regurgitation in all cases (n=9). Necropsy showed no evidence of tissue erosion and an excellent biocompatibility of the implanted devices. CONCLUSIONS: MLC, as a novel approach for catheter-based mitral valve repair, appeared feasible in this short-term preclinical model. Further studies with longer follow-up in a cardiomyopathic animal model are needed to verify the clinical feasibility and safety of MLC.

Changes of the Structural and Biomechanical Properties of the Bovine Pericardium after the Removal of α-Gal Epitopes by Decellularization and α-Galactosidase Treatment.

BACKGROUND: Bovine pericardium is one of the most widely used materials in bioprosthetic heart valves. Immunologic responses have been implicated as potential causes of limited durability of xenogenic valves. This study aimed to determine the effectiveness of decellularization and α-galactosidase (α-gal) to remove major xenoreactive antigens from xenogenic tissues. MATERIALS AND METHODS: Recombinant Bacteroides thetaiotaomicron (B. thetaiotaomicron) α-gal or decellularization, or both were used to remove α-gal from bovine pericardium. It was confirmed by α-gal-bovine serum albumin-based enzyme-linked immunosorbent assay (ELISA), high-performance anion exchange chromatography, flow cytometry, 3,3'-diaminobenzidine-staining, and lectin-based ELISA. The mechanical properties of bovine pericardium after decellularization or α-gal treatment were investigated by tests of tensile-strength, permeability, and compliance. Collagen fiber rearrangement was also evaluated by a 20,000× transmission electron microscope (TEM). RESULTS: Recombinant B. thetaiotaomicron α-gal could effectively remove α-gal from bovine pericardium B. thetaiotaomicron (0.1 U/mL, pH 7.2) while recombinant human α-gal removed it recombinant human α-gal (10 U/mL, pH 5.0). There was no difference in the mechanical properties of fresh and recombinant α-gal-treated bovine pericardium. Furthermore, the TEM findings demonstrated that recombinant α-gal made no difference in the arrangement of collagen fiber bundles with decellularization. CONCLUSION: Recombinant B. thetaiotaomicron α-gal effectively removed α-gal from bovine pericardium with a small amount under physiological conditions compared to human recombinant α-gal, which may alleviate the harmful xenoreactive immunologic responses of α-gal. Recombinant α-gal treatment had no adverse effects on the mechanical properties of bovine pericardium.

Does bilateral pedicle internal thoracic artery harvest increase the risk of mediastinitis?

PURPOSE: Bilateral in situ internal thoracic artery (ITA) bypassing may result in excellent myocardial revascularization without increasing the risk of deep sternal wound infection. Although there have been concerns with the use of pedicled bilateral ITA, the risk of infection may not be greater than the use of skeletonized ITA. MATERIALS AND METHODS: The present study was retrospectively undertaken to determine if pedicled BITA grafts are associated with a higher risk of sternal wound complications. A total of 207 patients who underwent bilateral ITA bypasses with or without existing diabetes mellitus, and 162 patients of those received bilateral pedicled ITA and 98 patients received unilateral ITA bypass grafts. RESULTS: No sternal wound complications were noted in either the bilateral ITA or unilateral left ITA groups. CONCLUSION: Bilateral pedicled ITA harvesting was not associated with a greater incidence of infectious sternal complications compared to patients receiving unilateral ITA bypass grafts.

7-Ketocholesterol upregulates interleukin-6 via mechanisms that are distinct from those of tumor necrosis factor-alpha, in vascular smooth muscle cells.

This study investigated the effects of 7-ketocholesterol on interleukin (IL)-6 expression in vascular smooth muscle cells (VSMC). Among the 7 IL examined, only IL-6 transcript was increased by 7-ketocholesterol treatment in human aorta smooth muscle cells. IL-6 transcripts increased up to 24 h after treatment with 7-ketocholesterol, and this effect was profoundly repressed by treatment with p38 MAPK inhibitors and to a lesser extent JNK inhibitors. 7alpha-Hydroxycholesterol, 27-hydroxycholesterol or cholesterol, however, did not induce IL-6 expression. Mechanisms of IL-6 induction by 7-ketocholesterol were investigated in comparison with tumor necrosis factor (TNF)-alpha. Whereas TNF-alpha activated IL-6 promoter, which was impaired by p38 MAPK inhibitors or by mutation in the NF-kappaB-binding site within the promoter region, 7-ketocholesterol did not affect IL-6 promoter activity. Instead, this oxysterol slowed degradation of IL-6 mRNA and increased the amount of cytoplasmic HuR. 7-ketocholesterol significantly increased the amount of intracellular IL-6 protein in the presence of brefeldin A. 7-Ketocholesterol also enhanced IL-6 release from VSMC. IL-6 release by 7-ketocholesterol, although significant, was not as remarkable as that induced by TNF-alpha. These data suggest that 7-ketocholesterol upregulates IL-6 via mechanisms distinct from TNF-alpha and contributes to the intra- and extracellular IL-6 deposits within the vasculature.

Apigenin inhibits immunostimulatory function of dendritic cells: Implication of immunotherapeutic adjuvant.

Apigenin, one of the most common flavonoids, has been shown to possess anti-inflammatory, anticarcinogenic, and free radical-scavenging properties. However, the influence of apigenin on the immunostimulatory effects and maturation of dendritic cells (DC) remains, for the most part, unknown. In this study, we have attempted to ascertain whether apigenin influences the expression of surface molecules, dextran uptake, cytokine production, and T-cell differentiation as well as the signaling pathways underlying these phenomena in murine bone marrow-derived DC. In the presence of apigenin, CD80, CD86, and major histocompatibility complex class I and II molecules, expressions on DC were significantly suppressed, and lipopolysaccharide (LPS)-induced interleukin (IL)-12 expression was impaired. The DC proved highly efficient at antigen capture, as evidenced by the observation of mannose receptor-mediated endocytosis in the presence of apigenin. The LPS-induced activation of mitogen-activated protein kinase, the nuclear translocation of its nuclear factor-kappaB p65 subunit, and the induction of the T-helper 1 response were all impaired in the presence of apigenin, whereas the cell-mediated immune response remained normal. These findings provide new insight into the immunopharmacological functions of apigenin and its effects on DC, and they may also prove useful in the development of adjuvant therapies for individuals suffering from acute or chronic DC-associated diseases.

Bidirectional cavopulmonary shunt as a rescue procedure for right ventricular endomyocardial fibrosis.

The surgical treatment for patients with endomyocardial fibrosis consists of resection of endocardial fibrotic tissue and replacement or repair of atrioventricular valve. Even after endocardiectomy and valvular remodeling, some patients exhibit very poor hemodynamic profile because of myocardial failure due to long-standing restriction of ventricle or ventricles. Here, we report a case of endomyocardial fibrosis in right ventricle who underwent endocardiectomy and valvular replacement followed by bi-directional cavopulmonary shunt to compensate weaning failure from cardiopulmonary bypass. The long-term outcome and the indication of bi-directional cavopulmonary shunt has not been confirmed, although it was effective for saving the life of patients with low cardiac output and acute right ventricular failure.