The REDUCE FMR Trial: A Randomized Sham-Controlled Study of Percutaneous Mitral Annuloplasty in Functional Mitral Regurgitation

Objectives This study sought to evaluate the effects of the Carillon device on mitral regurgitation severity and left ventricular remodeling. Background Functional mitral regurgitation (FMR) complicates heart failure with reduced ejection fraction and is associated with a poor prognosis. Methods In this blinded, randomized, proof-of-concept, sham-controlled trial, 120 patients receiving optimal heart failure medical therapy were assigned to a coronary sinus-based mitral annular reduction approach for FMR or sham. The pre-specified primary endpoint was change in mitral regurgitant volume at 12 months, measured by quantitative echocardiography according to an intention-to-treat analysis. Results Patients (69.8 ± 9.5 years of age) were randomized to either the treatment (n = 87) or the sham-controlled (n = 33) arm. There were no significant differences in baseline characteristics between the groups. In the treatment group, 73 of 87 (84%) had the device implanted. The primary endpoint was met, with a statistically significant reduction in mitral regurgitant volume in the treatment group compared to the control group (decrease of 7.1 ml/beat [95% confidence interval [CI]: −11.7 to −2.5] vs. an increase of 3.3 ml/beat [95% CI: −6.0 to 12.6], respectively; p = 0.049). Additionally, there was a significant reduction in left ventricular volumes in patients receiving the device versus those in the control group (left ventricular end-diastolic volume decrease of 10.4 ml [95% CI: −18.5 to −2.4] vs. an increase of 6.5 ml [95% CI: −5.1 to 18.2]; p = 0.03 and left ventricular end-systolic volume decrease of 6.2 ml [95% CI: −12.8 to 0.4] vs. an increase of 6.1 ml [95% CI: −1.42 to 13.6]; p = 0.04). Conclusions The Carillon device significantly reduced mitral regurgitant volume and left ventricular volumes in symptomatic patients with functional mitral regurgitation receiving optimal medical therapy. (Carillon Mitral Contour System for Reducing Functional Mitral Regurgitation [REDUCE FMR]; NCT02325830

A randomized double-blind trial of an interventional device treatment of functional mitral regurgitation in patients with symptomatic congestive heart failure-Trial design of the REDUCE FMR study

The Carillon Mitral Contour System has been studied in 3 nonrandomized trials in patients with symptomatic congestive heart failure and functional mitral regurgitation. The REDUCE FMR study is a uniquely designed, double-blind trial evaluating the impact of the Carillon device on reducing regurgitant volume, as well as assessing the safety and clinical efficacy of this device. Carillon is a coronary sinus-based indirect annuloplasty device. Eligible patients undergo an invasive venogram to assess coronary sinus vein suitability for the Carillon device. If the venous dimensions are suitable, they are randomized on a 3:1 basis to receive a device or not. Patients and assessors are blinded to the treatment assignment. The primary end point is the difference in regurgitant volume at 1 year between the implanted and nonimplanted groups. Other comparisons include clinical parameters such as heart failure hospitalizations, 6-minute walk test, Kansas City Cardiomyopathy Questionnaire (KCCQ), and other echocardiographic parameters. An exercise echo substudy will also be included

Low-Cost Precursors to Novel Hydrogen Storage Materials

From 2005 to 2010, The Dow Chemical Company (formerly Rohm and Haas Company) was a member of the Department of Energy Center of Excellence on Chemical Hydrogen Storage, which conducted research to identify and develop chemical hydrogen storage materials having the potential to achieve DOE performance targets established for on-board vehicular application. In collaboration with Center co-leads Los Alamos National Laboratory (LANL) and Pacific Northwest National Laboratory (PNNL), and other Center partners, Dow's efforts were directed towards defining and evaluating novel chemistries for producing chemical hydrides and processes for spent fuel regeneration. In Phase 1 of this project, emphasis was placed on sodium borohydride (NaBH{sub 4}), long considered a strong candidate for hydrogen storage because of its high hydrogen storage capacity, well characterized hydrogen release chemistry, safety, and functionality. Various chemical pathways for regenerating NaBH{sub 4} from spent sodium borate solution were investigated, with the objective of meeting the 2010/2015 DOE targets of $2-3/gal gasoline equivalent at the pump ($2-3/kg H{sub 2}) for on-board hydrogen storage systems and an overall 60% energy efficiency. With the September 2007 No-Go decision for NaBH{sub 4} as an on-board hydrogen storage medium, focus was shifted to ammonia borane (AB) for on-board hydrogen storage and delivery. However, NaBH{sub 4} is a key building block to most boron-based fuels, and the ability to produce NaBH{sub 4} in an energy-efficient, cost-effective, and environmentally sound manner is critical to the viability of AB, as well as many leading materials under consideration by the Metal Hydride Center of Excellence. Therefore, in Phase 2, research continued towards identifying and developing a single low-cost NaBH4 synthetic route for cost-efficient AB first fill, and conducting baseline cost estimates for first fill and regenerated AB using a variety of synthetic routes. This project utilized an engineering-guided R&D approach, which involved the rapid down-selection of a large number of options (chemical pathways to NaBH{sub 4}) to a smaller, more manageable number. The research began by conducting an extensive review of the technical and patent literature to identify all possible options. The down-selection was based on evaluation of the options against a set of metrics, and to a large extent occurred before experimentation was initiated. Given the vast amount of literature and patents that has evolved over the years, this approach helped to focus efforts and resources on the options with the highest technical and commercial probability of success. Additionally, a detailed engineering analysis methodology was developed for conducting the cost and energy-efficiency calculations. The methodology utilized a number of inputs and tools (Aspen PEA{trademark}, FCHTool, and H2A). The down-selection of chemical pathways to NaBH{sub 4} identified three options that were subsequently pursued experimentally. Metal reduction of borate was investigated in Dow's laboratories, research on electrochemical routes to NaBH{sub 4} was conducted at Pennsylvania State University, and Idaho National Laboratory researchers examined various carbothermal routes for producing NaBH{sub 4} from borate. The electrochemical and carbothermal studies did not yield sufficiently positive results. However, NaBH{sub 4} was produced in high yields and purities by an aluminum-based metal reduction pathway. Solid-solid reactive milling, slurry milling, and solution-phase approaches to metal reduction were investigated, and while both reactive milling and solution-phase routes point to fully recyclable processes, the scale-up of reactive milling processes to produce NaBH{sub 4} is expected to be difficult. Alternatively, a low-cost solution-phase approach to NaBH{sub 4} has been identified that is based on conventional process unit operations and should be amenable to scale-up. Numerous advances in AB synthesis have been made in recent years to improve AB yields and purities. Process analysis of several leading routes to AB (Purdue's formate-based metathesis route and PNNL's NH{sub 4}BH{sub 4}-based route) indicated the cost to produce first-fill AB to be on the order of $9-10/kg AB, assuming a NaBH{sub 4} cost of$5/kg for a 10,000 metric tons/year sized AB plant. The analysis showed that the dominant cost component for producing first-fill AB is the cost of the NaBH4 raw material. At this AB cost and assuming 2.5 moles hydrogen released per mole of AB, it may be possible to meet DOE's 2010 storage system cost target, but the 2015 target will likely require lower cost AB and demonstrates the importance of having a low-cost route to NaBH{sub 4}. Substantial progress has also been made to define feasible pathways for the regeneration of spent ammonia borane fuel

Assessment of left ventricular volumes and function by cine-MR imaging depending on the investigator’s experience

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