Autonomic regulation therapy to enhance myocardial function in heart failure patients: the ANTHEM-HFpEF study.

BackgroundApproximately half of the patients presenting with new-onset heart failure (HF) have HF with preserved left ventricular ejection fraction (HFpEF) and HF with mid-range left ventricular ejection fraction (HFmrEF). These patients have neurohormonal activation like that of HF with reduced ejection fraction; however, beta-blockers and angiotensin-converting enzyme inhibitors have not been shown to improve their outcomes, and current treatment for these patients is symptom based and empiric. Sympathoinhibition using parasympathetic stimulation has been shown to improve central and peripheral aspects of the cardiac nervous system, reflex control, induce myocyte cardioprotection, and can lead to regression of left ventricular hypertrophy. Beneficial effects of autonomic regulation therapy (ART) using vagus nerve stimulation (VNS) have also been observed in several animal models of HFpEF, suggesting a potential role for ART in patients with this disease.MethodsThe Autonomic Neural Regulation Therapy to Enhance Myocardial Function in Patients with Heart Failure and Preserved Ejection Fraction (ANTHEM-HFpEF) study is designed to evaluate the feasibility, tolerability, and safety of ART using right cervical VNS in patients with chronic, stable HFpEF and HFmrEF. Patients with symptomatic HF and HFpEF or HFmrEF fulfilling the enrolment criteria will receive chronic ART with a subcutaneous VNS system attached to the right cervical vagus nerve. Safety parameters will be continuously monitored, and cardiac function and HF symptoms will be assessed every 3 months during a post-titration follow-up period of at least 12 months.ConclusionsThe ANTHEM-HFpEF study is likely to provide valuable information intended to expand our understanding of the potential role of ART in patients with chronic symptomatic HFpEF and HFmrEF

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

The Radial Structure of the Cygnus Loop Supernova Remnant --- Possible evidence of a cavity explosion ---

We observed the North-East (NE) Limb toward the center region of the Cygnus Loop with the ASCA Observatory. We found a radial variation of electron temperature (kTe) and ionization timescale (log(\tau)) whereas no variation could be found for the abundances of heavy elements. In this paper, we re-analyzed the same data set and new observations with the latest calibration files. Then we constructed the precise spatial variations of kTe, log(\tau), and abundances of O, Ne, Mg, Si, and Fe over the field of view (FOV). We found a spatial variation not only in kTe and in log(\tau) but also in most of heavy elements. As described in Miyata et al. (1994), values of kTe increase and those of log(\tau) decrease toward the inner region. We found that the abundance of heavy elements increases toward the inner region. The radial profiles of O, Ne, and Fe show clear jump structures at a radius of 0.9 Rs, where Rs is the shock radius. Outside of 0.9 Rs, abundances of all elements are constant. On the contrary, inside of 0.9 Rs, abundances of these elements are 20--30 % larger than those obtained outside of 0.9 Rs. The radial profile of kTe also shows the jump structure at 0.9 Rs. This means that the hot and metal rich plasma fills the volume inside of 0.9 Rs. We concluded that this jump structure was the possible evidence for the pre-existing cavity produced by the precursor. If the ejecta fills inside of 0.9 Rs, the total mass of the ejecta was roughly 4\Msun. We then estimated the main-sequence mass to be roughly 15\Msun, which supports the massive star in origin of the Cygnus Loop supernova remnant and the existence of a pre-existing cavity.Comment: 37 pages, 14 figures. Accepted for publication of Ap

Chronic Low-Level Vagus Nerve Stimulation Improves Long-Term Survival in Salt-Sensitive Hypertensive Rats

Chronic hypertension (HTN) affects more than 1 billion people worldwide, and is associated with an increased risk of cardiovascular disease. Despite decades of promising research, effective treatment of HTN remains challenging. This work investigates vagus nerve stimulation (VNS) as a novel, device-based therapy for HTN treatment, and specifically evaluates its effects on long-term survival and HTN-associated adverse effects. HTN was induced in Dahl salt-sensitive rats using a high-salt diet, and the rats were randomly divided into two groups: VNS (n = 9) and Sham (n = 8), which were implanted with functional or non-functional VNS stimulators, respectively. Acute and chronic effects of VNS therapy were evaluated through continuous monitoring of blood pressure (BP) and ECG via telemetry devices. Autonomic tone was quantified using heart rate (HR), HR variability (HRV) and baroreflex sensitivity (BRS) analysis. Structural cardiac changes were quantified through gross morphology and histology studies. VNS significantly improved the long-term survival of hypertensive rats, increasing median event-free survival by 78% in comparison to Sham rats. Acutely, VNS improved autonomic balance by significantly increasing HRV during stimulation, which may lead to beneficial chronic effects of VNS therapy. Chronic VNS therapy slowed the progression of HTN through an attenuation of SBP and by preserving HRV. Finally, VNS significantly altered cardiac structure, increasing heart weight, but did not alter the amount of fibrosis in the hypertensive hearts. These results suggest that VNS has the potential to improve outcomes in subjects with severe HTN

THE KNIFE EDGE TEST AS A WAVEFRONT SENSOR (IMAGE PROCESSING).

An algorithm to reduce data from the knife edge test is given. The method is an extension of the theory of single sideband holography to second order effects. Application to phase microscopy is especially useful because a troublesome second order term vanishes when the knife edge does not attenuate the unscattered radiation probing the specimen. The algorithm was tested by simulation of an active optics system that sensed and corrected small (less than quarter wavelength) wavefront errors. Convergence to a null was quadratic until limited by detector-injected noise in signal. The best form of the algorithm used only a Fourier transform of the smoothed detector record, a filtering of the transform, an inverse transform, and an arctangent solving for the phase of the input wavefront deformation. Iterations were helpful only for a Wiener filtering of the data record that weighted down Fourier amplitudes smaller than the mean noise level before analysis. The simplicity and sensitivity of this wavefront sensor makes it a candidate for active optic control of small-angle light scattering in space. In real time optical processing a two dimensional signal can be applied as a voltage to a deformable mirror and be received as an intensity modulation at an output plane. Combination of these features may permit a real time null test. Application to electron microscopy should allow the finding of defocus, astigmatism, and spherical aberrations for single micrographs at 0.2 nm resolution, provided a combination of specimen and support membrane is used that permits some a priori knowledge. For some thin specimens (up to nearly 100 atom layers thick) the left-right symmetry of diffraction should allow reconstruction of the wave-front deformations caused by the specimen with double the bandpass used in each image