Vagus nerve stimulation: A new approach to reduce heart failure

Autonomic imbalance with increased adrenergic and reduced parasympathetic activity is involved in the development and progress of heart failure (HF). Experimental data have demonstrated that stimulation of the vagus nerve is able to reverse ventricular remodeling of the failing heart. There is also evidence that increasing parasympathetic activity may stimulate the production of nitric oxide, and reduce the devastating inflammatory process involved in HF. Vagus nerve stimulation (VNS) has been successfully applied for many years to treat drug resistant epilepsy. The first study of right vagus stimulation in patients with advance HF has proven the feasibility and safety of this new approach. Long term follow-up of increased vagal tone over 12 months with a specially designed stimulating system (CardioFit, BioControl, Yehud, Israel) has demonstrated that symptoms of HF can be significantly diminished, left ventricular ejection fraction increased, and ventricular volumes reduced. These recently published data are very promising and may offer another approach for patients with advanced HF already treated with optimal medical therapy. A prospective randomized trial with a larger patient cohort is needed to confirm these beneficial results of VNS. (Cardiol J 2010; 17, 6: 638-643

Why Should We Care About CARE-HF?

Previous trials of cardiac resynchronization therapy (CRT) have suggested that this therapy can significantly improve functional class and exercise capacity during short-term follow-up. The impact of this therapy on morbidity and mortality has only recently been reported. The Cardiac Resynchronization-Heart Failure (CARE-HF) study has definitively shown that CRT significantly reduces mortality (36%, p < 0.002) in patients with NYHA functional class III and IV heart failure and ventricular dyssynchrony. This study also shows that CRT reverses ventricular remodeling and improves myocardial performance progressively for at least 18 months. In heart failure patients, the CARE-HF and Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) (the earlier major morbidity/mortality trial) studies together show the unequivocal benefit for CRT therapy and CRT therapy with back-up defibrillation to significantly reduce mortality and hospitalization compared with optimal medical therapy. Both studies suggest the benefit of adding the implantable cardiac defibrillator to CRT devices, as over one-third of deaths in the CRT-pacemaker arm of both the COMPANION and CARE-HF studies were sudden

Cardiac resynchronization therapy restores optimal atrioventricular mechanical timing in heart failure patients with ventricular conduction delay

AbstractObjectivesWe characterized the relationship between systolic ventricular function and left ventricular (LV) end-diastolic pressure (LVEDP) in patients with heart failure (HF) and baseline asynchrony during ventricular stimulation.BackgroundThe role of preload in the systolic performance improvement that can be obtained in HF patients with LV stimulation is uncertain.MethodsWe measured the maximum rate of increase of LV pressure, LVEDP, aortic pulse pressure (PP) and the atrioventricular mechanical latency (AVL) between left atrial systole and LV pressure onset in 39 patients with HF. Two subgroups were identified: “responder” if PP improved, or “nonresponder.”ResultsMaximum hemodynamic improvement occurred at an atrioventricular (AV) delay that did not decrease LVEDP. Left ventricular and biventricular (BV) stimulation increased systolic hemodynamics significantly, despite no significant increase in LVEDP. All parameters decreased when the LVEDP was decreased by shorter AV delay. Left ventricular and BV stimulation provided better hemodynamics than right ventricular (RV) stimulation. For the nonresponder subgroup, systolic hemodynamics only worsened during AV delay shortening. For the responder subgroup, optimum PP was achieved when AVL was near zero.ConclusionsRestoration of optimal left atrial-ventricular mechanical timing partly contributes to the hemodynamic improvements observed in this patient subgroup. However, preload alone cannot explain the differences seen between RV and BV stimulation and the contradictory PP decreases even at maximal preload in the nonresponder subgroup. These results may be explained by a site-dependent mechanism such as the degree of ventricular synchrony. Caution should be taken in these patients when optimizing AV delays using echocardiography techniques that focus on LV inflow

Properties of the Ideal Ginzburg-Landau Vortex Lattice

The magnetization curves M(H) for ideal type-II superconductors and the maximum, minimum, and saddle point magnetic fields of the vortex lattice are calculated from Ginzburg-Landau theory for the entire ranges of applied magnetic fields Hc1 <= H < Hc2 or inductions 0 <= B < Hc2 and Ginzburg-Landau parameters sqrt(1/2) <= kappa <= 1000. Results for the triangular and square flux-line lattices are compared with the results of the circular cell approximation. The exact magnetic field B(x,y) and magnetization M(H, kappa) are compared with often used approximate expressions, some of which deviate considerably or have limited validity. Useful limiting expressions and analytical interpolation formulas are presented.Comment: 11 pages, 8 figure

Comparison of symptomatic and functional responses to vagus nerve stimulation in ANTHEM-HF, INOVATE-HF, and NECTAR-HF

AIMS: Clinical studies of vagal nerve stimulation (VNS) for heart failure with reduced ejection fraction have had mixed results to date. We sought to compare VNS delivery and associated changes in symptoms and function in autonomic regulation therapy via left or right cervical vagus nerve stimulation in patients with chronic heart failure (ANTHEM-HF), increase of vagal tone in heart failure (INOVATE-HF), and neural cardiac therapy for heart failure (NECTAR-HF) for hypothesis generation. METHODS AND RESULTS: Descriptive statistics were used to analyse data from the public domain for differences in proportions using Pearson\u27s chi-square test, differences in mean values using Student\u27s unpaired t-test, and differences in changes of mean values using two-sample t-tests. Guideline-directed medical therapy recommendations were similar across studies. Fewer patients were in New York Heart Association 3, and baseline heart rate (HR) was higher in ANTHEM-HF. In INOVATE-HF, VNS was aimed at peripheral neural targets, using closed-loop delivery that required synchronization of VNS to R-wave sensing by an intracardiac lead. Pulse frequency was low (1-2 Hz) because of a timing schedule allowing ≤3 pulses of VNS following at most 25% of detected R waves. NECTAR-HF and ANTHEM-HF used open-loop VNS delivery (i.e. independent of any external signal) aimed at both central and peripheral targets. In NECTAR-HF, VNS delivery at 20 Hz caused off-target effects that limited VNS up-titration in a majority of patients. In ANTHEM-HF, VNS delivery at 10 Hz allowed up-titration until changes in HR dynamics were confirmed. Six months after VNS titration, significant improvements in both HR and HR variability occurred only in ANTHEM-HF. When ANTHEM-HF and NECTAR-HF were compared, greater improvements from baseline were observed in ANTHEM-HF in standard deviation in normal-to-normal R-R intervals (94 ± 26 to 111 ± 50 vs. 146 ± 48 to 130 ± 52 ms; P \u3c 0.001), left ventricular ejection fraction (32 ± 7 to 37 ± 0.4 vs. 31 ± 6 to 33 ± 6; P \u3c 0.05), and Minnesota Living with Heart Failure mean score (40 ± 14 to 21 ± 10 vs. 44 ± 22 to 36 ± 21; P \u3c 0.002). When compared with INOVATE-HF, greater improvement in 6-min walk distance was observed in ANTHEM-HF (287 ± 66 to 346 ± 78 vs. 304 ± 111 to 334 ± 111 m; P \u3c 0.04). CONCLUSIONS: In this post-hoc analysis, differences in patient demographics were seen and may have caused the differential responses in symptoms and function observed in association with VNS. Major differences in technology platforms, neural targets, VNS delivery, and HR and HR variability responses could have also potentially played a very important role. Further study is underway in a randomized controlled trial with these considerations in mind

First detection of the atomic O18 isotope in the mesosphere and lower thermosphere of Earth

In the lower atmosphere of Earth, oxygen contains a higher fraction of the heavy O18 isotope than ocean water does (Dole effect). This isotopic enrichment is a signature of biological activity, set by the equilibrium between oxygenic photosynthesis and respiratory metabolisms in terrestrial and oceanic ecosystems. While the mixing between stratospheric and tropospheric oxygen leads to a slow isotopic homogenization, little is known about the isotopic oxygen enrichment in the mesosphere and thermosphere of Earth. In situ measurements from rocket-borne air samplers are limited to altitudes below the mesopause, while higher layers have only been accessible through the analysis of the oxidation of ancient cosmic spherules. Here we report the detection of the far-infrared fine-structure lines (3P1<-3P2 and 3P0<-3P1) of O18 in absorption against the Moon, and determine the O16/O18 ratio in atomic oxygen from the mesosphere and lower thermosphere in absorption. After correcting for isotopic exchange between atomic and molecular oxygen, our values for the bulk O16/O18 ratio of 468 and 382 in February and November 2021, respectively, fall significantly below that found in solar wind samples (530±2), and encompass, within uncertainties, the corresponding ratios pertaining to the Dole effect in the troposphere (487), and those found in stratospheric ozone (429 to 466). We show that with existing technology, future, more sensitive measurements will allow us to monitor deviations from isotopic homogeneity in the mesosphere and lower thermosphere of Earth by remote sensing. We demonstrate that the collisional excitation of the fine-structure levels of the P3 ground-state triplet of O18 may compete with isotopic exchange reactions, implying a deviation from the Boltzmann distribution that would be established under local thermodynamic equilibrium

Advances in our clinical understanding of autonomic regulation therapy using vagal nerve stimulation in patients living with heart failure

The ANTHEM-HF, INOVATE-HF, and NECTAR-HF clinical studies of autonomic regulation therapy (ART) using vagus nerve stimulation (VNS) systems have collectively provided dose-ranging information enabling the development of several working hypotheses on how stimulation frequency can be utilized during VNS for tolerability and improving cardiovascular outcomes in patients living with heart failure (HF) and reduced ejection fraction (HFrEF). Changes in heart rate dynamics, comprising reduced heart rate (HR) and increased HR variability, are a biomarker of autonomic nerve system engagement and cardiac control, and appear to be sensitive to VNS that is delivered using a stimulation frequency that is similar to the natural operating frequency of the vagus nerve. Among prior studies, the ANTHEM-HF Pilot Study has provided the clearest evidence of autonomic engagement with VNS that was delivered using a stimulation frequency that was within the operating range of the vagus nerve. Achieving autonomic engagement was accompanied by improvement from baseline in six-minute walk duration (6MWD), health-related quality of life, and left ventricular EF (LVEF), over and above those achieved by concomitant guideline-directed medical therapy (GDMT) administered to counteract harmful neurohormonal activation, with relative freedom from deleterious effects. Autonomic engagement and positive directional changes have persisted over time, and an exploratory analysis suggests that improvement in autonomic tone, symptoms, and physical capacity may be independent of baseline NT-proBNP values. Based upon these encouraging observations, prospective, randomized controlled trials examining the effects on symptoms and cardiac function as well as natural history have been warranted. A multi-national, large-scale, randomized, controlled trial is well underway to determine the outcomes associated with ART using autonomic nervous system engagement as a guide for VNS delivery

Electrostatic potential in a superconductor

The electrostatic potential in a superconductor is studied. To this end Bardeen's extension of the Ginzburg-Landau theory to low temperatures is used to derive three Ginzburg-Landau equations - the Maxwell equation for the vector potential, the Schroedinger equation for the wave function and the Poisson equation for the electrostatic potential. The electrostatic and the thermodynamic potential compensate each other to a great extent resulting into an effective potential acting on the superconducting condensate. For the Abrikosov vortex lattice in Niobium, numerical solutions are presented and the different contributions to the electrostatic potential and the related charge distribution are discussed.Comment: 19 pages, 11 figure