Classification of Heart Failure According to Ejection Fraction JACC Review Topic of the Week

The recent U.S. Food and Drug Administration expanded indication for sacubitril/valsartan introduces a new potential taxonomy for heart failure, with no reference to "preserved" ejection fraction but referring to "below normal" ejection fraction as those most likely to benefit. This review summarizes the evolution of nomenclature in heart failure and examines evidence showing that patients with ejection fraction in the "mid range" may benefit from neurohormonal blockade similar to those with more severely reduced

Advances in Digital Health Research

Social media and emerging mobile technologies have sparked radical shifts in human behavior, with people worldwide spending an average of 2 hours and 15 minutes daily on social networks. Facebook, Instagram, and Twitter have more than 2 billion users globally. Social networking site use has risen dramatically by all age groups, with the highest use among 18-29 year olds (see Figure below). Every second, Twitter users send 6,000 tweets, amounting to 500 million tweets per day. Instagram users post approximately 95 million photos, generating 4.2 billion likes, each day. A newer platform, Snapchat, has 178 million daily users, 60% of whom are under 25 years of age. They share an average of 3 billion snaps, or rapidly vanishing photos, every day. Researchers at Penn are turning these Tweets, posts, and snaps into innovative data sources that hold vital clues about behaviors, emotions, preferences, opinions, and social networks—all with potential implications for population health. Through the analysis of keywords, images, phrases, emoticons, likes, and hashtags, Penn teams are turning troves of digital information into human-centered health interventions and educational initiatives.https://repository.upenn.edu/publichealth_databriefs/1004/thumbnail.jp

The Opioid Crisis

Opioid use and addiction have reached epidemic proportions in Philadelphia, making drug overdose involving opioids a leading cause of death. Both pharmaceutical and illicit opioids contribute to this crisis. Opioid sales in Philadelphia more than doubled between 2000 and 2012, and health care providers continue to prescribe opioid pain medication in greater quantities than medically appropriate. The peak age group for overdoses is 45-54, an older age group than previously seen. Over-prescribing of opioids contributes to the recruitment of adults into drug dependence. While use of opioid pain medications usually does not lead to opioid use disorder, four out of five heroin users nationwide transitioned from original use of prescription medications. Heroin is easy to obtain, potent and cheap compared to prescription pain medications. There are estimated to be at least 70,000 heroin users in Philadelphia.https://repository.upenn.edu/publichealth_databriefs/1003/thumbnail.jp

Valsartan for attenuating disease evolution in early sarcomeric hypertrophic cardiomyopathy: the design of the Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy (VANISH) trial

Background: Hypertrophic cardiomyopathy (HCM) is often caused by sarcomere gene mutations, resulting in left ventricular hypertrophy (LVH), myocardial fibrosis, and increased risk of sudden cardiac death and heart failure. Studies in mouse models of sarcomeric HCM demonstrated that early treatment with an angiotensin receptor blocker (ARB) reduced development of LVH and fibrosis. In contrast, prior human studies using ARBs for HCM have targeted heterogeneous adult cohorts with well-established disease. The VANISH trial is testing the safety and feasibility of disease-modifying therapy with an ARB in genotyped HCM patients with early disease. Methods: A randomized, placebo-controlled, double-blind clinical trial is being conducted in sarcomere mutation carriers, 8 to 45 years old, with HCM and no/minimal symptoms, or those with early phenotypic manifestations but no LVH. Participants are randomly assigned to receive valsartan 80 to 320 mg daily (depending on age and weight) or placebo. The primary endpoint is a composite of 9 z-scores in domains representing myocardial injury/hemodynamic stress, cardiac morphology, and function. Total z-scores reflecting change from baseline to final visits will be compared between treatment groups. Secondary endpoints will assess the impact of treatment on mutation carriers without LVH, and analyze the influence of age, sex, and genotype. Conclusions: The VANISH trial is testing a new strategy of disease modification for treating sarcomere mutation carriers with early HCM, and those at risk for its development. In addition, further insight into disease mechanisms, response to therapy, and phenotypic evolution will be gained

Craters Hosting Radar-Bright Deposits in Mercury's North Polar Region: Areas of Persistent Shadow Determined from MESSENGER Images

Radar-bright features near Mercury's poles were discovered in Earth-based radar images and proposed to be water ice present in permanently shadowed areas. Images from MESSENGER's one-year primary orbital mission provide the first nearly complete view of Mercury’s north polar region, as well as multiple images of the surface under a range of illumination conditions. We find that radar-bright features near Mercury's north pole are associated with locations persistently shadowed in MESSENGER images. Within 10 degrees of the pole, almost all craters larger than 10 km in diameter host radar-bright deposits. There are several craters located near Mercury's north pole with sufficiently large diameters to enable long-lived water ice to be thermally stable at the surface within regions of permanent shadow. Craters located farther south also host radar-bright deposits and show a preference for cold-pole longitudes; thermal models suggest that a thin insulating layer is required to cover these deposits if the radar-bright material consists predominantly of longlived water ice. Many small (less than 10 km diameter) and low-latitude (extending southward to 66 degrees N) craters host radar-bright material, and water ice may not be thermally stable in these craters for ~1 Gy, even beneath an insulating layer. The correlation of radar-bright features with persistently shadowed areas is consistent with the deposits being composed of water ice, and future thermal modeling of small and low-latitude craters has the potential to further constrain the nature, source, and timing of emplacement of the radar-bright material

Insights into the subsurface structure of the Caloris basin, Mercury, from assessments of mechanical layering and changes in long-wavelength topography

The volcanic plains that fill the Caloris basin, the largest recognized impact basin on Mercury, are deformed by many graben and wrinkle ridges, among which the multitude of radial graben of Pantheon Fossae allow us to resolve variations in the depth extent of associated faulting. Displacement profiles and displacement-to-length scaling both indicate that faults near the basin center are confined to a ~ 4-km-thick mechanical layer, whereas faults far from the center penetrate more deeply. The fault scaling also indicates that the graben formed in mechanically strong material, which we identify with dry basalt-like plains. These plains were also affected by changes in long-wavelength topography, including undulations with wavelengths of up to 1300 km and amplitudes of 2.5 to 3 km. Geographic correlation of the depth extent of faulting with topographic variations allows a first-order interpretation of the subsurface structure and mechanical stratigraphy in the basin. Further, crosscutting and superposition relationships among plains, faults, craters, and topography indicate that development of long-wavelength topographic variations followed plains emplacement, faulting, and much of the cratering within the Caloris basin. As several examples of these topographic undulations are also found outside the basin, our results on the scale, structural style, and relative timing of the topographic changes have regional applicability and may be the surface expression of global-scale interior processes on Mercury

Insights into the subsurface structure of the Caloris basin, Mercury, from assessments of mechanical layering and changes in long-wavelength topography

The volcanic plains that fill the Caloris basin, the largest recognized impact basin on Mercury, are deformed by many graben and wrinkle ridges, among which the multitude of radial graben of Pantheon Fossae allow us to resolve variations in the depth extent of associated faulting. Displacement profiles and displacement-to-length scaling both indicate that faults near the basin center are confined to a ~ 4-km-thick mechanical layer, whereas faults far from the center penetrate more deeply. The fault scaling also indicates that the graben formed in mechanically strong material, which we identify with dry basalt-like plains. These plains were also affected by changes in long-wavelength topography, including undulations with wavelengths of up to 1300 km and amplitudes of 2.5 to 3 km. Geographic correlation of the depth extent of faulting with topographic variations allows a first-order interpretation of the subsurface structure and mechanical stratigraphy in the basin. Further, crosscutting and superposition relationships among plains, faults, craters, and topography indicate that development of long-wavelength topographic variations followed plains emplacement, faulting, and much of the cratering within the Caloris basin. As several examples of these topographic undulations are also found outside the basin, our results on the scale, structural style, and relative timing of the topographic changes have regional applicability and may be the surface expression of global-scale interior processes on Mercury

Comparison of Areas in Shadow from Imaging and Altimetry in the North Polar Region of Mercury and Implications for Polar Ice Deposits

Earth-based radar observations and results from the MESSENGER mission have provided strong evidence that permanently shadowed regions near Mercury's poles host deposits of water ice. MESSENGER's complete orbital image and topographic datasets enable Mercury's surface to be observed and modeled under an extensive range of illumination conditions. The shadowed regions of Mercury's north polar region from 65 deg N to 90 deg N were mapped by analyzing Mercury Dual Imaging System (MDIS) images and by modeling illumination with Mercury Laser Altimeter (MLA) topographic data. The two independent methods produced strong agreement in identifying shadowed areas. All large radar-bright deposits, those hosted within impact craters greater than or equal to 6 km in diameter, collocate with regions of shadow identified by both methods. However, only approximately 46% of the persistently shadowed areas determined from images and approximately 43% of the permanently shadowed areas derived from altimetry host radar-bright materials. Some sizable regions of shadow that do not host radar-bright deposits experience thermal conditions similar to those that do. The shadowed craters that lack radar-bright materials show a relation with longitude that is not related to the thermal environment, suggesting that the Earth-based radar observations of these locations may have been limited by viewing geometry, but it is also possible that water ice in these locations is insulated by anomalously thick lag deposits or that these shadowed regions do not host water ice