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

Temporal profile and mechanisms of the prompt sympathoexcitation following coronary ligation in Wistar rats

Our aim was to assess the timing and mechanisms of the sympathoexcitation that occurs immediately after coronary ligation. We recorded thoracic sympathetic (tSNA) and phrenic activities, heart rate (HR) and perfusion pressure in Wistar rats subjected to either ligation of the left anterior descending coronary artery (LAD) or Sham operated in the working heart-brainstem preparation. Thirty minutes after LAD ligation, tSNA had increased (basal: 2.5±0.2 µV, 30 min: 3.5±0.3 µV), being even higher at 60 min (5.2±0.5 µV, P<0.01); while no change was observed in Sham animals. HR increased significantly 45 min after LAD (P<0.01). Sixty minutes after LAD ligation, there was: (i) an augmented peripheral chemoreflex - greater sympathoexcitatory response (50, 45 and 27% of increase to 25, 50 and 75 µL injections of NaCN 0.03%, respectively, when compared to Sham, P<0.01); (ii) an elevated pressor response (32±1 versus 23±1 mmHg in Sham, P<0.01) and a reduced baroreflex sympathetic gain (1.3±0.1 versus Sham 2.0±0.1%.mmHg-1, P<0.01) to phenylephrine injection; (iii) an elevated cardiac sympathetic tone (ΔHR after atenolol: -108±8 versus -82±7 bpm in Sham, P<0.05). In contrast, no changes were observed in cardiac vagal tone and bradycardic response to both baroreflex and chemoreflex between LAD and Sham groups. The immediate sympathoexcitatory response in LAD rats was dependent on an excitatory spinal sympathetic cardiocardiac reflex, whereas at 3 h an angiotensin II type 1 receptor mechanism was essential since Losartan curbed the response by 34% relative to LAD rats administered saline (P<0.05). A spinal reflex appears key to the immediate sympathoexcitatory response after coronary ligation. Therefore, the sympathoexcitatory response seems to be maintained by an angiotensinergic mechanism and concomitant augmentation of sympathoexcitatory reflexes

Search for same-sign top-quark pair production at √s = 7 TeV and limits on flavour changing neutral currents in the top sector

An inclusive search for same-sign top-quark pair production in pp collisions at √s = 7 TeV is performed using a data sample recorded with the CMS detector in 2010, corresponding to an integrated luminosity of 35 pb^(−1). This analysis is motivated by recent studies of pp → tt reporting mass-dependent forward-backward asymmetries larger than expected from the standard model. These asymmetries could be due to Flavor Changing Neutral Currents (FCNC) in the top sector induced by t-channel exchange of a massive neutral vector boson (Z′). Models with such a Z′ also predict enhancement of same-sign top-pair production in pp or pp collisions. Limits are set as a function of the Z′ mass and its couplings to u and t quarks. These limits disfavour the FCNC interpretation of the Tevatron results

Measurement of the ratio of the 3-jet to 2-jet cross sections in pp collisions at √s = 7 TeV

A measurement of the ratio of the inclusive 3-jet to 2-jet cross sections as a function of the total jet transverse momentum, H_T, in the range 0.20.5 TeV. This measurement extends to an H_T range that has not been explored before

A search for excited leptons in pp collisions at √s = 7 TeV

A search for excited leptons is carried out with the CMS detector at the LHC, using 36 pb^(−1) of pp collision data recorded at √s = 7 TeV. The search is performed for associated production of a lepton and an oppositely charged excited lepton pp→ℓℓ^*, followed by the decay ℓ^*→ℓγ, resulting in the ℓℓγ final state, where ℓ=e,μ. No excess of events above the standard model expectation is observed. Interpreting the findings in the context of ℓ^* production through four-fermion contact interactions and subsequent decay via electroweak processes, first upper limits are reported for ℓ^* production at this collision energy. The exclusion region in the compositeness scale Λ and excited lepton mass M_(ℓ*) parameter space is extended beyond previously established limits. For Λ=M_(ℓ*), excited lepton masses are excluded below 1070 GeV/c^2 for e^* and 1090 GeV/c^2 for μ^* at the 95% confidence level

Search for first generation scalar leptoquarks in the eνjj channel in pp collisions at √s = 7 Tev

A search for pair-production of first generation scalar leptoquarks is performed in the final state containing an electron, a neutrino, and at least two jets using proton–proton collision data at √s = 7 TeV. The data were collected by the CMS detector at the LHC, corresponding to an integrated luminosity of 36 pb^(−1). The number of observed events is in good agreement with the predictions for standard model processes. Prior CMS results in the dielectron channel are combined with this electron + neutrino search. A 95% confidence level combined lower limit is set on the mass of a first generation scalar leptoquark at 339 GeV for β=0.5, where β is the branching fraction of the leptoquark to an electron and a quark. These results represent the most stringent direct limits to date for values of β greater than 0.05

Long-range and short-range dihadron angular correlations in central PbPb collisions at √sNN = 2.76 TeV

First measurements of dihadron correlationsfor charged particles are presented for central PbPb collisions at a nucleon-nucleon center-of-mass energy of 2.76TeV over a broad range in relative pseudorapidity (∆η) and the full range of relative azimuthal angle (∆ϕ). The data were collected with the CMS detector, at the LHC. A broadening of the away-side (∆ϕ ≈ π) azimuthal correlation is observed at all ∆η, as compared to the measurements in pp collisions. Furthermore, long-range dihadron correlations in ∆η are observed for particles with similar ϕ values. This phenomenon, also known as the “ridge”, persists up to at least |∆η| = 4. For particles with transverse momenta (pT) of2-4 GeV/c, the ridge is found to be most prominent when these particles are correlated with particles of pT = 2-6 GeV/c, and to be much reduced when paired with particles of pT = 10-12 GeV/c