Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Solution of Integral Equation with Neutrosophic Rectangular Triple Controlled Metric Spaces

In this paper, we introduce the notion of neutrosophic rectangular triple-controlled metric space, relaxing the symmetry requirement of neutrosophic metric spaces, by replacing triangular inequalities with rectangular inequalities, and prove fixed point theorems. We have derived several interesting results for contraction mappings supplemented with non-trivial examples. The derived results have been applied to prove the existence of a unique analytical solution as well as a closed form of the unique solution to the integral equation

CRT-D Therapy in Patients with Decompensated NYHA Class-Four CHF

Background. ACC-HRS Guidelines for Cardiac Resynchronization Therapy ICD implantation (CRT-D) do not include patients with advanced nonambulatory NYHA class-four CHF due to an expectation of limited survival. There is little data available from these large multicenter randomized studies to support or refute this claim. Purpose. We evaluated the outcomes of patients with advanced nonambulatory NYHA class-four CHF who received CRT-D devices as an attempt to improve the clinical status and promote hospital discharge. Methods. Sixteen (of our six hundred and seventy CRT-D patients) were classified as advanced nonambulatory NYHA Class four inotrope/vasodilator/diuretic-dependent patients. These patients were analyzed retrospectively for weaning success to oral medications, hospital discharge, hemodynamic stability, and survival over eighteen months. Results. Thirteen of sixteen patients were discharged to home within two weeks of implantation. The survival to hospital discharge, as well as at six, twelve, and eighteen months was positive (ninety-four percent, seventy-five percent, sixty-nine percent, sixty-nine percent, resp.). The groups showed significant improvements in systolic blood pressure, renal function, left ventricular ejection fraction, and CHF class. Conclusion. CRT-D in advanced nonambulatory NYHA four patients proved feasible and beneficial. These findings suggest that the strategy merits further study

Coherent population trapping in Raman-pulse atom interferometry

Raman pulse atom interferometry is an important modality for precision measurements of inertial forces and tests of fundamental physics. Typical Raman atom optics use two coherent laser fields applied at gigahertz-scale detunings from optical resonance, so that spontaneous emission produces a minor or negligible source of decoherence. An additional consequence of spontaneous emission is coherent population trapping (CPT). We show that CPT produces coherences and population differences which induce systematic effects in Raman pulse atom interferometers. We do not believe that CPT has been previously identified as an error mechanism in Raman pulse atom interferometry. We present an experimental characterization of CPT coherences and population differences induced in laser-cooled cesium atoms by application of Raman pulses at detunings near 1 GHz, commensurate with detunings used in several precision measurement experiments. We are not aware of previous demonstrations of CPT-induced population difference. We argue that CPT effects could induce phase shifts of several milliradians in magnitude for typical experimental parameters and stipulate that these errors can be suppressed by propagation direction reversal in Raman interferometer-based precision measurements.Charles Stark Draper Laboratory (Office of Education)Charles Stark Draper Laboratory (IR&D program