Designing comparative effectiveness trials of surgical ablation for atrial fibrillation: experience of the Cardiothoracic Surgical Trials Network.

Objective: Since the introduction of the cut-and-sew Cox maze procedure for atrial fibrillation, there has been substantial innovation in techniques for ablation. Use of alternative energy sources for ablation simplified the procedure and has resulted in dramatic increase in the number of patients with atrial fibrillation treated by surgical ablation. Despite its increasingly widespread adoption, there is lack of rigorous clinical evidence to establish this procedure as an effective clinical therapy.

Eu(3+)-mediated polymerization of benzenetetracarboxylic acid studied by spectroscopy, temperature-dependent calorimetry, and density functional theory.

Thermodynamic parameters for the complexation of Eu(3+) with pyromellitic acid (1,2,4,5-benzenetetracarboxylic acid, BTC) as a model system for polymerizable metal-complexing humic acids were determined using temperature-dependent time-resolved laser-induced fluorescence spectroscopy (TRLFS) and isothermal titration calorimetry (ITC). At low metal and ligand concentrations (<50 μM Eu(3+), <1 mM BTC), a 1:1 monomeric Eu-BTC complex was identified in the range of 25-60 °C. At elevated concentrations (>500 μM Eu(3+) and BTC) a temperature-dependent polymerization was observed, where BTC monomers are linked via coordinating shared Eu(3+) ions.

The next decade in mechanical assist: advances that will help the patient and the doctor.

Purpose Of Review: Significant technological advances have occurred in mechanical assist devices over the past decade. With improving hemodynamics and durability, ventricular assist devices (VADs) are being implanted with increasing frequency. Yet, several VAD-specific morbidities and technological challenges, which are reviewed, continue to limit the number of devices that are currently implanted.

Structural integrity of {alpha}-helix H12 in translation initiation factor eIF5B is critical for 80S complex stability.

Translation initiation factor eIF5B promotes GTP-dependent ribosomal subunit joining in the final step of the translation initiation pathway. The protein resembles a chalice with the α-helix H12 forming the stem connecting the GTP-binding domain cup to the domain IV base. Helix H12 has been proposed to function as a rigid lever arm governing domain IV movements in response to nucleotide binding and as a molecular ruler fixing the distance between domain IV and the G domain of the factor.

Mitral valve repair in heart failure: five-year follow-up from the mitral valve replacement stratum of the Acorn randomized trial.

Objective: The study objective was to evaluate the long-term (5-year) safety and efficacy of mitral valve surgery with and without the CorCap cardiac support device (Acorn Cardiovascular, St Paul, Minn) in patients with dilated cardiomyopathy and New York Heart Association class II-IV heart failure.

Background: The Acorn trial provided a unique opportunity to assess the long-term safety and efficacy of mitral valve surgery because clinical visits and echocardiograms (read by a core laboratory) were completed for 5 years of follow-up. Further, this study provided follow-up data on the long-term effect of the CorCap cardiac support device as an adjunct to mitral valve surgery.

Implantable ventricular assist device exchange with focused intravascular deairing techniques.

As ventricular assist devices are increasingly adopted and widely implemented as a highly effective therapy for end-stage heart disease, extended utilization periods for destination therapy or bridge-to-transplantation have created the possibility of device failure, infection, or thrombosis, requiring challenging implant exchanges. A major problem in these operations is the risk of air embolization, particularly in a nonsternotomy approach that precludes access to the outflow aortic graft and to the ascending aorta. We report a minimally invasive, nonsternotomy HeartMate II implantable left ventricular assist device (LVAD) exchange, using peripheral cardiopulmonary support and a novel approach to continuous intravascular ascending aortic air removal.

Quantitative mitral valve modeling using real-time three-dimensional echocardiography: technique and repeatability.

Background: Real-time three-dimensional (3D) echocardiography has the ability to construct quantitative models of the mitral valve (MV). Imaging and modeling algorithms rely on operator interpretation of raw images and may be subject to observer-dependent variability. We describe a comprehensive analysis technique to generate high-resolution 3D MV models and examine interoperator and intraoperator repeatability in humans.

Ischemic mitral regurgitation: a quantitative three-dimensional echocardiographic analysis.

Background: A comprehensive three-dimensional echocardiography based approach is applied to preoperative mitral valve (MV) analysis in patients with ischemic mitral regurgitation (IMR). This method is used to characterize the heterogeneous nature of the pathologic anatomy associated with IMR.

Methods: Intraoperative real-time three-dimensional transesophageal echocardiograms of 18 patients with IMR (10 with anterior, 8 with inferior infarcts) and 17 patients with normal MV were analyzed.

Pulsatile left ventricular assist devices: what is the role in the modern era?

With the widespread use of continuous-flow ventricular assist devices (VADs), the role of pulsatile VADs remain in question. In acute cardiogenic shock, pulsatile VADs maximize perfusion pressure, restore end organ perfusion, and maximally unload the pulmonary circulation and right heart. In addition, pulsatile left VADs allow for easy conversion to biventricular support using one platform, in the case of acute right ventricular failure.

When a parent goes to war: effects of parental deployment on very young children and implications for intervention.

Young children (birth through 5 years of age) are disproportionately represented in U.S. military families with a deployed parent.

First fluorescence spectroscopic investigation of Am(III) complexation with an organic carboxylic ligand, pyromellitic acid.

For the first time Am(III) complexation with a small organic ligand could be identified and characterized with time-resolved laser-induced fluorescence spectroscopy (TRLFS) at room temperature and trace metal concentration. With pyromellitic acid (1,2,4,5-benzene-tetracarboxylic acid, BTC) as ligand spectroscopic characteristics for the Am-BTC complex system were determined at pH 5.0, an ionic strength of 0.

Sex, aging, and preexisting cerebral ischemic disease in patients with aortic stenosis.

Background: Patients undergoing cardiac surgery have a high frequency of preexisting cerebral ischemic lesions, the presence of which appears to predict cognitive sequelae. Patients undergoing aortic valve replacement for aortic stenosis (AS) incur an exceptionally high risk for perioperative cerebral ischemia. The extreme risk in this subgroup may arise from the preexisting burden of cerebral ischemic disease.

Use of the AB5000 ventricular assist device in cardiogenic shock after acute myocardial infarction.

Background: The mortality rate of patients experiencing acute myocardial infarction (AMI) complicated by cardiogenic shock remains high. After conventional therapies have failed, ventricular assist devices (VADs) have been used to bridge patients to recovery or transplantation.

Methods: A voluntary US registry was established to track all patients implanted with the AB5000 VAD.

Genetic interception and structural characterization of thiopeptide cyclization precursors from Bacillus cereus.

The pyridine core of the thiocillins has long been postulated to arise from a late-stage tail-to-tail condensation of two dehydroalanines. Genetic disruption of tclM, a proposed "Diels-Alderase", allowed isolation of acyclic precursors to this pyridine ring. The isolated products possess the full cohort of post-translational modifications that are normally displayed by the thiocillins, including dehydrobutyrines, thiazoles, C-terminal decarboxylation, and the two previously unconfirmed dehydroalanines.

Management of prosthetic valves during ventricular assist device implantation.

Background: An increasing number of patients requiring ventricular assist devices (VAD) have had previous valvular corrections, including valve repair and valve replacement with mechanical or bioprosthetic valves. The operative and peri-operative management of these patients has been varied.

Methods: A retrospective study of VADs between January 1994 and June 2008 revealed 10 patients with previous prosthetic valves requiring management during and after VAD placement.

Limb ischemia during femoral cannulation for cardiopulmonary support.

Objectives: Extracorporeal membrane oxygenation and extracorporeal cardiopulmonary support (ECMO/CPS) are potentially life-saving techniques for patients with cardiopulmonary collapse. Complications include lower extremity ischemia from femoral artery cannulation. We examined the outcomes of patients placed on ECMO/CPS, including the rate of limb ischemia.

Thiazolyl peptide antibiotic biosynthesis: a cascade of post-translational modifications on ribosomal nascent proteins.

Antibiotics of the thiocillin, GE2270A, and thiostrepton class, which block steps in bacterial protein synthesis, contain a trithiazolyl (tetrahydro)pyridine core that provides the architectural constraints for high affinity binding to either the 50 S ribosomal subunit or elongation factor Tu. These mature antibiotic scaffolds arise from a cascade of post-translational modifications on 50-60-residue prepeptide precursors that trim away the N-terminal leader sequences (approximately 40 residues) while the C-terminal 14-18 residues are converted into the mature scaffold. In the producing microbes, the genes encoding the prepeptide open reading frames are flanked in biosynthetic clusters by genes encoding post-translational modification enzymes that carry out lantibiotic-type dehydrations of Ser and Thr residues to dehydroamino acid side chains, cyclodehydration and oxidation of cysteines to thiazoles, and condensation of two dehydroalanine residues en route to the (tetrahydro)pyridine core.

Manipulation of thiocillin variants by prepeptide gene replacement: structure, conformation, and activity of heterocycle substitution mutants.

Bacillus cereus ATCC 14579 converts the C-terminal 14 residues of a 52-mer prepeptide into a related set of eight variants of the thiocillin subclass of thiazolyl peptide antibiotics by a cascade of post-translational modifications that alter 13 of those 14 residues. We have introduced prepeptide gene variants into a knockout strain to conduct an alanine scan of all 14 progenitor residues, as well as a serine scan of the six cysteine residues that are converted to thiazoles in the mature natural product. No mature scaffolds were detected for the S1A and S10A mutants, consistent with their roles as the source of the pyridine core.

Mitral valve surgery in advanced heart failure.

The appropriateness and timing of mitral valve surgery in patients with advanced heart failure and severe mitral regurgitation remains controversial. Recent surgical results provide evidence for beneficial effects on left ventricular remodeling and functional capacity. Given the absence of randomized trials comparing the outcomes of mitral valve surgery to medical therapy, however, clinical decision making regarding surgery for these fragile patients poses a dilemma to thoughtful clinicians.

Generation of thiocillin variants by prepeptide gene replacement and in vivo processing by Bacillus cereus.

The thiocillins are natural-product antibiotics derived from ribosomally encoded peptides that undergo extensive posttranslational modifications to yield the mature trithiazolylpyridine-containing macrocyclic compound. Poor pharmacokinetic properties have prevented the clinical use of these highly potent antibiotics. Through in vivo manipulation of the gene responsible for production of the thiocillin precursor peptide, we have generated 65 novel thiocillin variants, allowing us to explore structure-activity relationships involved in both precursor peptide maturation and antibiotic activity.

INTERMACS: interval analysis of registry data.

Background: The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) is an NIH-sponsored registry of US FDA-approved mechanical circulatory support devices (MCSDs) used for destination therapy, bridge to transplantation (BTT), or recovery of the heart. INTERMACS data were analyzed through the most recent quarter ending March 31, 2008.

Study Design: INTERMACS variables include demographics, patient outcomes (survival and adverse events), hemodynamic data, and laboratory values.

Mechanisms of recurrent functional mitral regurgitation after mitral valve repair in nonischemic dilated cardiomyopathy: importance of distal anterior leaflet tethering.

Background: Recurrent functional mitral regurgitation (MR) has been reported after mitral valve repair with annuloplasty in patients with dilated cardiomyopathy, but the mechanism is not understood completely. The authors sought to identify abnormalities of the mitral valve and left ventricle that are associated with recurrent MR after mitral annuloplasty.

Method And Results: In 104 patients with idiopathic dilated cardiomyopathy who underwent annuloplasty for functional MR, basal mitral anterior leaflet angle, distal mitral anterior leaflet angle (ALAtip), posterior leaflet angle, coaptation depth, tenting area, mitral annular dimensions, left ventricular volumes, and MR severity were quantified by echocardiography before surgery and at 6-month intervals after it.

Early planned institution of biventricular mechanical circulatory support results in improved outcomes compared with delayed conversion of a left ventricular assist device to a biventricular assist device.

Objective: It is generally accepted that patients who require biventricular assist device support have poorer outcomes than those requiring isolated left ventricular assist device support. However, it is unknown how the timing of biventricular assist device insertion affects outcomes. We hypothesized that planned biventricular assist device insertion improves survival compared with delayed conversion of left ventricular assist device support to biventricular assist device support.