Contemporary Management of Secondary Mitral Regurgitation

Secondary mitral regurgitation (SMR) is a common occurrence in patients with heart failure with reduced ejection fraction. Moderate-severe or severe SMR is associated with increased mortality and hospitalisations from heart failure. Medical and cardiac resynchronisation therapies have been the only treatments proven to improve prognosis in this patient population. The Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy (COAPT) and the Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation (MITRA-FR) RCTs evaluated transcatheter mitral valve repair with MitraClip for treatment of SMR in addition to medical therapy and they had divergent results. The COAPT trial demonstrated that a reduction in SMR with MitraClip resulted in reduced mortality and heart failure hospitalisations along with improved symptoms and quality of life in appropriately selected patients. The MITRA-FR trial did not show any benefit from using MitraClip for patients with SMR. This article summarises the differences in these two trials and suggests a contemporary approach to the management of SMR

Why has positive inotropy failed in chronic heart failure? Lessons from prior inotrope trials.

Current pharmacological therapies for heart failure with reduced ejection fraction are largely either repurposed anti-hypertensives that blunt overactivation of the neurohormonal system or diuretics that decrease congestion. However, they do not address the symptoms of heart failure that result from reductions in cardiac output and reserve. Over the last few decades, numerous attempts have been made to develop and test positive cardiac inotropes that improve cardiac haemodynamics. However, definitive clinical trials have failed to show a survival benefit. As a result, no positive inotrope is currently approved for long-term use in heart failure. The focus of this state-of-the-art review is to revisit prior clinical trials and to understand the causes for their findings. Using the learnings from those experiences, we propose a framework for future trials of such agents that maximizes their potential for success. This includes enriching the trials with patients who are most likely to derive benefit, using biomarkers and imaging in trial design and execution, evaluating efficacy based on a wider range of intermediate phenotypes, and collecting detailed data on functional status and quality of life. With a rapidly growing population of patients with advanced heart failure, the epidemiologic insignificance of heart transplantation as a therapeutic intervention, and both the cost and morbidity associated with ventricular assist devices, there is an enormous potential for positive inotropic therapies to impact the outcomes that matter most to patients

The impact of seismic noise produced by wind turbines on seismic borehole measurements

Seismic signals produced by wind turbines can have an adverse effect on seismological measurements up to distances of several kilometres. Based on numerical simulations of the emitted seismic wave field, we study the effectivity of seismic borehole installations as a way to reduce the incoming noise. We analyse the signal amplitude as a function of sensor depth and investigate effects of seismic velocities, damping parameters and geological layering in the subsurface. Our numerical approach is validated by real data from borehole installations affected by wind turbines. We demonstrate that a seismic borehole installation with an adequate depth can effectively reduce the impact of seismic noise from wind turbines in comparison to surface installations. Therefore, placing the seismometer at greater depth represents a potentially effective measure to improve or retain the quality of the recordings at a seismic station. However, the advantages of the borehole decrease significantly with increasing signal wavelength.</p

Impurity and strain effects on the magnetotransport of La1.85Sr0.15Cu(1-y)Zn(y)O4 films

The influence of zinc doping and strain related effects on the normal state transport properties(the resistivity, the Hall angle and the orbital magneto- resistance(OMR) is studied in a series of La1.85Sr0.15Cu(1-y)Zn(y)O4 films with values of y between 0 and 0.12 and various degrees of strain induced by the mismatch between the films and the substrate. The zinc doping affects only the constant term in the temperature dependence of cotangent theta but the strain affects both the slope and the constant term, while their ratio remains constant.OMR is decreased by zinc doping but is unaffected by strain. The ratio delta rho/(rho*tan^2 theta) is T-independent but decreases with impurity doping. These results put strong constraints on theories of the normal state of high- temperature superconductors

Myocarditis Associated with Immune Checkpoint Inhibitors: An Expert Consensus on Data Gaps and a Call to Action.

Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for cancer. Due to the mechanism of action of ICIs, inflammatory reactions against normal tissue were an anticipated side effect of these agents; these immune-related adverse events have been documented and are typically low grade and manageable. Myocarditis has emerged as an uncommon but potentially life-threatening adverse reaction in patients treated with ICIs. Assessment and characterization of ICI-associated myocarditis is challenging because of its low incidence and protean manifestations. Nevertheless, the seriousness of ICI-associated myocarditis justifies a coordinated effort to increase awareness of this syndrome, identify patients who may be at risk, and enable early diagnosis and appropriate treatment. The Checkpoint Inhibitor Safety Working Group, a multidisciplinary committee of academic, industry, and regulatory partners, convened at a workshop hosted by Project Data Sphere, LLC, on December 15, 2017. This meeting aimed to evaluate the current information on ICI-associated myocarditis, determine methods to collect and share data on this adverse reaction, and establish task forces to close the identified knowledge gaps. In this report, we summarize the workshop findings and proposed steps to address the impact of ICI-associated myocarditis in patients with cancer

What’s Next for Acute Heart Failure Research?

Each year over one million patients with acute heart failure (AHF) present to a United States emergency department (ED). The vast majority are hospitalized for further management. The length of stay and high postdischarge event rate in this cohort have changed little over the past decade. Therapeutic trials have failed to yield substantive improvement in postdischarge outcomes; subsequently, AHF care has changed little in the past 40 years. Prior research studies have been fragmented as either “inpatient” or “ED-based.” Recognizing the challenges in identification and enrollment of ED patients with AHF, and the lack of robust evidence to guide management, an AHF clinical trials network was developed. This network has demonstrated, through organized collaboration between cardiology and emergency medicine, that many of the hurdles in AHF research can be overcome. The development of a network that supports the collaboration of acute care and HF researchers, combined with the availability of federally funded infrastructure, will facilitate more efficient conduct of both explanatory and pragmatic trials in AHF. Yet many important questions remain, and in this document our group of emergency medicine and cardiology investigators have identified four high-priority research areas

Magnetotransport in the Normal State of La1.85Sr0.15Cu(1-y)Zn(y)O4 Films

We have studied the magnetotransport properties in the normal state for a series of La1.85Sr0.15Cu(1-y)Zn(y)O4 films with values of y, between 0 and 0.12. A variable degree of compressive or tensile strain results from the lattice mismatch between the substrate and the film, and affects the transport properties differently from the influence of the zinc impurities. In particular, the orbital magnetoresistance (OMR) varies with y but is strain-independent. The relations for the resistivity and the Hall angle and the proportionality between the OMR and tan^2 theta are followed about 70 K. We have been able to separate the strain and impurity effects by rewriting the above relations, where each term is strain-independent and depends on y only. We also find that changes in the lattice constants give rise to closely the same fractional changes in other terms of the equation.The OMR is more strongly supressed by the addition of impurities than tan^2 theta. We conclude that the relaxation ratethat governs Hall effect is not the same as for the magnetoresistance. We also suggest a correspondence between the transport properties and the opening of the pseudogap at a temperature which changes when the La-sr ratio changes, but does not change with the addition of the zinc impurities

Clinical and Research Considerations for Patients with Hypertensive Acute Heart Failure

Management approaches for patients in the emergency department (ED) who present with acute heart failure (AHF) have largely focused on intravenous diuretics. Yet, the primary pathophysiologic derangement underlying AHF in many patients is not solely volume overload. Patients with hypertensive AHF (H-AHF) represent a clinical phenotype with distinct pathophysiologic mechanisms that result in elevated ventricular filling pressures. To optimize treatment response and minimize adverse events in this subgroup, we propose that clinical management be tailored to a conceptual model of disease based on these mechanisms. This consensus statement reviews the relevant pathophysiology, clinical characteristics, approach to therapy, and considerations for clinical trials in ED patients with H-AHF

Orbital Magnetoresistance in the LaSrCuO System

Measurements of resistivity, Hall effect, and magnetoresistance have been made on seven c-axis oriented thin-film specimens of La(2-x)Sr(x)CuO(4) with values of x from 0.048 to 0.275, and one specimen that also contains Nd. The orbital magnetoresistance is found not to be proportional to the square of the tangent of the Hall angle except for values of x near 0.15 above about 80K. For smaller values of x the temperature dependence of the magnetoresistance is different, but quite similar in the various specimens, in spite of large differences in resistivity, Hall coefficient, and Hall angle.Comment: LaTeX, 14 pages, 4 embedded color eps figure