bluuebunny/crossref_metadata_2025 huggingface dataset:
Physiological basis of interactive responses to temperature and salinity in coastal marine invertebrate: Implications for responses to warming
Authors: Torres Gabriela , Charmantier Guy , Wilcockson David , Harzsch Steffen , Giménez Luis
Published: May 2021

Developing physiological mechanistic models to predict species’ responses to climate‐driven environmental variables remains a key endeavor in ecology. Such approaches are challenging, because they require linking physiological processes with fitness and contraction or expansion in species’ distributions. We explore those links for coastal marine species, occurring in regions of freshwater influence (ROFIs) and exposed to changes in temperature and salinity. First, we evaluated the effect of temperature on hemolymph osmolality and on the expression of genes relevant for osmoregulation in larvae of the shore crab Carcinus maenas. We then discuss and develop a hypothetical model linking osmoregulation, fitness, and species expansion/contraction toward or away from ROFIs. In C. maenas, high temperature led to a threefold increase in the capacity to osmoregulate in the first and last larval stages (i.e., those more likely to experience low salinities). This result matched the known pattern of survival for larval stages where the negative effect of low salinity on survival is mitigated at high temperatures (abbreviated as TMLS). Because gene expression levels did not change at low salinity nor at high temperatures, we hypothesize that the increase in osmoregulatory capacity (OC) at high temperature should involve post‐translational processes. Further analysis of data suggested that TMLS occurs in C. maenas larvae due to the combination of increased osmoregulation (a physiological mechanism) and a reduced developmental period (a phenological mechanisms) when exposed to high temperatures. Based on information from the literature, we propose a model for C. maenas and other coastal species showing the contribution of osmoregulation and phenological mechanisms toward changes in range distribution under coastal warming. In species where the OC increases with temperature (e.g., C. maenas larvae), osmoregulation should contribute toward expansion if temperature increases; by contrast in those species where osmoregulation is weaker at high temperature, the contribution should be toward range contraction.
Linking alternative reproductive tactics and habitat selection in Northern chamois
Authors: Corlatti Luca , Cotza Antonella , Nelli Luca
Published: May 2021

In polygynous ungulates, males may achieve fertilization through the use of alternative reproductive tactics (ARTs), discrete phenotypic variations evolved to maximize fitness. ARTs are often associated with different male spatial strategies during the rut, from territoriality to female‐following. Although variation in space use patterns of rutting male ungulates is known to be largely affected by the spatial distribution of females, information on the year‐round habitat selection of alternative reproductive types is scant. Here, we investigate the seasonal variation in habitat choice of a large mammal with ARTs (territoriality and nonterritoriality), the Northern chamois Rupicapra rupicapra. Global Positioning System (GPS) data on 28 adult males were collected between February 2010 and December 2013 in the Gran Paradiso National Park (Italy) and used to fit resource selection functions to explore the ART‐specific use of key topographic features, such as elevation, aspect, and slope, and vegetation phenology expressed as NDVI values. Territorial and nonterritorial chamois profoundly differed in their habitat selection not only during the rutting season. Compared to nonterritorial males, territorial males used lower elevations in summer and autumn, preferred southern slopes in spring and summer, and used steeper areas in summer but not in winter. We found no difference in seasonal selection of NDVI values between males adopting ARTs. Our results suggest that territorial males tend to occupy warmer, lower‐food‐quality habitats in late spring and summer, whereas nonterritorial males are free to follow and exploit vegetation phenology and more favorable temperatures. Different patterns of habitat selection may reflect different trade‐offs between the optimization of energy balances throughout the year and the increase of mating opportunities during the rut in males adopting alternative reproductive tactics.
Why do Argos satellite tags stop relaying data?
Authors: Hays Graeme C. , Laloë Jacques‐Olivier , Rattray Alex , Esteban Nicole
Published: May 2021

Satellite tracking of animals is very widespread across a range of marine, freshwater, and terrestrial taxa. Despite the high cost of tags and the advantages of long deployments, the reasons why tracking data from tags stop being received are rarely considered, but possibilities include shedding of the tag, damage to the tag (e.g., the aerial), biofouling, battery exhaustion, or animal mortality.

We show how information relayed via satellite tags can be used to assess why tracking data stop being received. As a case study to illustrate general approaches that are broadly applicable across taxa, we examined data from Fastloc‐GPS Argos tags deployed between 2012 and 2019 on 78 sea turtles of two species, the green turtle (Chelonia mydas) and the hawksbill turtle (Eretmochelys imbricata).

Tags transmitted for a mean of 267 days (SD = 113 days, range: 26–687 days, median = 251 days). In 68 of 78 (87%) cases, battery failure was implicated as the reason why tracking data stopped being received. Some biofouling of the saltwater switches, which synchronize transmissions with surfacing, was evident in a few tags but never appeared to be the reason that data reception ceased.

Objectively assessing why tags fail will direct improvements to tag design, setup, and deployment regardless of the study taxa. Assessing why satellite tags stop transmitting will also inform on the fate of tagged animals, for example, whether they are alive or dead at the end of the study, which may allow improved estimates of survival rates.
Nocturnal incubation recess and flushing behavior by duck hens
Authors: Croston Rebecca , Peterson Sarah H. , Hartman C. Alex , Herzog Mark P. , Feldheim Cliff L. , Casazza Michael L. , Ackerman Joshua T.
Published: May 2021

Incubating birds must balance the needs of their developing embryos with their own physiological needs, and many birds accomplish this by taking periodic breaks from incubation. Mallard (Anas platyrhynchos) and gadwall (Mareca strepera) hens typically take incubation recesses in the early morning and late afternoon, but recesses can also take place at night. We examined nocturnal incubation recess behavior for mallard and gadwall hens nesting in Suisun Marsh, California, USA, using iButton temperature dataloggers and continuous video monitoring at nests. Fourteen percent of all detected incubation recesses (N = 13,708) were nocturnal and took place on 20% of nest‐days (N = 8,668). Video monitoring showed that hens covered their eggs with down feathers when they initiated a nocturnal recess themselves as they would a diurnal recess, but they left the eggs uncovered in 94% of the nocturnal recesses in which predators appeared at nests. Thus, determining whether or not eggs were left uncovered during a recess can provide strong indication whether the recess was initiated by the hen (eggs covered) or a predator (eggs uncovered). Because nest temperature decreased more rapidly when eggs were left uncovered versus covered, we were able to characterize eggs during nocturnal incubation recesses as covered or uncovered using nest temperature data. Overall, we predicted that 75% of nocturnal recesses were hen‐initiated recesses (eggs covered) whereas 25% of nocturnal recesses were predator‐initiated recesses (eggs uncovered). Of the predator‐initiated nocturnal recesses, 56% were accompanied by evidence of depredation at the nest during the subsequent nest monitoring visit. Hen‐initiated nocturnal recesses began later in the night (closer to morning) and were shorter than predator‐initiated nocturnal recesses. Our results indicate that nocturnal incubation recesses occur regularly (14% of all recesses) and, similar to diurnal recesses, most nocturnal recesses (75%) are initiated by the hen rather than an approaching predator.
The effect of nest temperature on growth and survival in juvenile Great TitsParus major
Authors: Corregidor‐Castro Alejandro , Jones Owen R.
Published: May 2021

For birds, maintaining an optimal nest temperature is critical for early‐life growth and development. Temperatures deviating from this optimum can affect nestling growth and fledging success with potential consequences on survival and lifetime reproductive success. It is therefore particularly important to understand these effects in relation to projected temperature changes associated with climate change.

Targets set by the 2015 Paris Agreement aim to limit temperature increases to 2°C, and, with this in mind, we carried out an experiment in 2017 and 2018 where we applied a treatment that increased Great TitParusmajornest temperature by approximately this magnitude (achieving an increase of 1.6°C, relative to the control) during the period from hatching to fledging to estimate how small temperature differences might affect nestling body size and weight at fledging and fledging success.

We recorded hatching and fledging success and measured skeletal size (tarsus length) and body mass at days 5, 7, 10, and 15 posthatch in nestlings from two groups of nest boxes: control and heated (+1.6°C).

Our results show that nestlings in heated nest boxes were 1.6% smaller in skeletal size at fledging than those in the cooler control nests, indicating lower growth rates in heated boxes, and that their weight was, in addition, 3.3% lower.

These results suggest that even fairly small changes in temperature can influence phenotype and postfledging survival in cavity‐nesting birds. This has the potential to affect the population dynamics of these birds in the face of ongoing climatic change, as individuals of reduced size in colder winters may suffer from decreased fitness.
Density dependence of daily activity in three ungulate species
Authors: Ramirez Juan Ignacio , Zwerts Joeri A. , van Kuijk Marijke , Iacobelli Palma , Li Xuqing , Herdoiza Natalie , Jansen Patrick A.
Published: May 2021

Daily activity in herbivores reflects a balance between finding food and safety. The safety‐in‐numbers theory predicts that living in higher population densities increases safety, which should affect this balance. High‐density populations are thus expected to show a more even distribution of activity—that is, spread—and higher activity levels across the day. We tested these predictions for three ungulate species; red deer (Cervus elaphus), roe deer (Capreolus capreolus), and wild boar (Sus scrofa). We used camera traps to measure the level and spread of activity across ten forest sites at the Veluwe, the Netherlands, that widely range in ungulate density. Food availability and hunting levels were included as covariates. Daily activity was more evenly distributed when population density was higher for all three species. Both deer species showed relatively more feeding activity in broad daylight and wild boar during dusk. Activity level increased with population density only for wild boar. Food availability and hunting showed no correlation with activity patterns. These findings indicate that ungulate activity is to some degree density dependent. However, while these patterns might result from larger populations feeling safer as the safety‐in‐numbers theory states, we cannot rule out that they are the outcome of greater intraspecific competition for food, forcing animals to forage during suboptimal times of the day. Overall, this study demonstrates that wild ungulates adjust their activity spread and level based on their population size.
Pond Acoustic Sampling Scheme: A draft protocol for rapid acoustic data collection in small waterbodies
Authors: Abrahams Carlos , Desjonquères Camille , Greenhalgh Jack
Published: May 2021

Freshwater conservation is vital to the maintenance of global biodiversity. Ponds are a critical, yet often under‐recognized, part of this, contributing to overall ecosystem functioning and diversity. They provide habitats for a range of aquatic, terrestrial, and amphibious life, often including rare and declining species.

Effective, rapid, and accessible survey methods are needed to enable evidence‐based conservation action, but freshwater taxa are often viewed as “difficult”—and few specialist surveyors are available. Datasets on ponds are therefore limited in their spatiotemporal coverage.

With the advent of new recording technologies, acoustic survey methods are becoming increasingly available to researchers, citizen scientists, and conservation practitioners. They can be an effective and noninvasive approach for gathering data on target species, assemblages, and environmental variables. However, freshwater applications are lagging behind those in terrestrial and marine spheres, and as an emergent method, research studies have employed a multitude of different sampling protocols.

We propose the Pond Acoustic Sampling Scheme (PASS), a simple protocol to allow a standardized minimal sample to be collected rapidly from small waterbodies, alongside environmental and methodological metadata. This sampling scheme can be incorporated into a variety of survey designs and is intended to allow access to a wide range of participants, without requiring complicated or prohibitively expensive equipment.

Adoption of this sampling protocol would enable consistent sound recordings to be gathered by researchers and conservation organizations, and allow the development of landscape‐scale surveys, data sharing, and collaboration within an expanding freshwater ecoacoustic community—rather than individual approaches that produce incompatible datasets. The compilation of standardized data would improve the prospects for effective research into the soundscapes of small waterbodies and aid freshwater conservation efforts.
Development of dry‐nano‐polishing technique using reactive ion etching for ultra thin titanium wafer
Authors: Chino Teruya , Watanabe Yuta , Tsukiyama Yosuke , Sohgawa Masayuki , Abe Takashi
Published: May 2021

In this study, we developed a dry‐nano‐polishing technique using reactive ion etching for ultra thin titanium wafer. The surface of titanium coated with photoresist is polished by reactive ion etching using SF6 /C4F8 gas. Etching speed of titanium and photoresist were adjusted to close to each other by changing temperature and ratio of SF6 /C4F8 gas. By etching titanium under these conditions, the smooth surface shape of the resist was transferred to titanium. By combining with photolithography, it is possible to polish a specific part.
Supercritical CO2‐Tailored 2D Oxygen‐doped Amorphous Carbon Nitride for Enhanced Photocatalytic Activity
Authors: Du Lina , Tian Qingyong , Zheng Xiaoli , Guo Wenjing , Liu Wei , Zhou Yannan , Shi Feng , Xu Qun
Published: May 2021

Simultaneously adjusting the surface, crystallographic and electronic structures of nanomaterials provide a new avenue for rational design of advanced photocatalyst yet it is challenging. In this work, a surface and structural engineering strategy is developed to simultaneously realize the 2D amorphous structure and oxygen (O)‐doping in graphitic carbon nitride (g–C3N4) via the assistance of supercritical carbon dioxide (SC CO2). The 2D O‐doped amorphous g–C3N4 nanosheets display greatly enhanced photocatalytic CO2 reduction and methylene blue degradation performances. The synthesis method as well as the mechanism of the enhanced photocatalytic activity was investigated, wherein the introduction of 2D amorphous structure and O dopant in the g–C3N4 contributes to the increased surface area, abundant active sites, wider visible‐light absorption range and efficient charge separation property, and thus the outstanding photocatalytic activities can be obtained. Its photocatalytic CH4 evolution rate and MB degradation rete are 5.1 and 7.0 times enhancement over bulk crystalline g–C3N4, respectively. This work presents a great promising way for designing and developing advanced photocatalysts.
Iron deficiency in heart failure
Authors: Loncar Goran , Obradovic Danilo , Thiele Holger , von Haehling Stephan , Lainscak Mitja
Published: May 2021

Iron deficiency is a major heart failure co‐morbidity present in about 50% of patients with stable heart failure irrespective of the left ventricular function. Along with compromise of daily activities, it also increases patient morbidity and mortality, which is independent of anaemia. Several trials have established parenteral iron supplementation as an important complimentary therapy to improve patient well‐being and physical performance. Intravenous iron preparations, in the first‐line ferric carboxymaltose, demonstrated in previous clinical trials superior clinical effect in comparison with oral iron preparations, improving New York Heart Association functional class, 6 min walk test distance, peak oxygen consumption, and quality of life in patients with chronic heart failure. Beneficial effect of iron deficiency treatment on morbidity and mortality of heart failure patients is waiting for conformation in ongoing trials. Although the current guidelines for treatment of chronic and acute heart failure acknowledge importance of iron deficiency correction and recommend intravenous iron supplementation for its treatment, iron deficiency remains frequently undertreated and insufficiently diagnosed in setting of the chronic heart failure. This paper highlights the current state of the art in the pathophysiology of iron deficiency, associations with heart failure trajectory and outcome, and an overview of current guideline‐suggested treatment options.
Association between sacubitril/valsartan initiation and real‐world health status trajectories over 18 months in heart failure with reduced ejection fraction
Authors: Thomas Merrill , Khariton Yevgeniy , Fonarow Gregg C. , Arnold Suzanne V. , Hill Larry , Nassif Michael E. , Chan Paul S. , Butler Javed , Thomas Laine , DeVore Adam D. , Hernandez Adrian F. , Albert Nancy M. , Patterson J. Herbert , Williams Fredonia B. , Spertus John A.
Published: May 2021

Aims

Improving the health status (symptoms, function, and quality of life) of patients with heart failure with reduced ejection fraction (HFrEF) is a primary treatment goal. Angiotensin receptor neprilysin inhibitors (ARNI) improve short‐term health status in clinical practice, but the sustainability of these improvements is unknown.

Methods and results

In CHAMP‐HF, a multicentre observational study of outpatients with HFrEF, patients initiated on ARNI were propensity score matched 1:2 to patients not using ARNI with Cox regression modelling time to ARNI initiation, adjusted for sociodemographic and clinical variables, medical history, medications, and baseline Kansas City Cardiomyopathy Questionnaire (KCCQ) scores. Repeated measures models for the overall KCCQ score and each domain compared the health status trajectories of patients initiated on ARNI vs. not. Among 3930 participants, 746 (19.0%) began ARNI, of whom 576 were matched to 1152 non‐ARNI patients. Prior to matching, participants initiated on ARNI were younger, non‐Hispanic, had lower EFs, more commonly had a history of ventricular arrhythmia, were less likely to be taking an ACEI/ARB, and more likely to be treated with beta‐blockers and mineralocorticoid receptor antagonists. There were no differences after matching. In the matched cohort, participants initiated on ARNI experienced improved health status by 3 months that persisted through 12 months [KCCQ Overall Summary Score (OSS) = 73.4 vs. 70.8; P < 0.001], with the largest benefit observed in the KCCQ Quality of Life domain (68.7 vs. 64.7; P < 0.001). Similar health status benefits were noted through 18 months (KCCQ‐OSS = 73.9 vs. 71.3; P < 0.001). A responder analysis showed that 12 patients would need to be initiated on ARNI for one to experience at least a large improvement (≥10 points) in health status benefit at 12 months.

Conclusions

In outpatient practice, ARNI therapy was associated with improved health status by 3 months and continued to 18 months after initiating therapy.
Derivation and validation of a two‐variable index to predict 30‐day outcomes following heart failure hospitalization
Authors: Averbuch Tauben , Lee Shun Fu , Mamas Mamas Andreas , Oz Urun Erbas , Perez Richard , Connolly Stuart James , Ko Dennis Tien‐Wei , Van Spall Harriette Gillian Christine
Published: May 2021

Background

The LACE index—length of stay (L), acuity (A), Charlson co‐morbidities (C), and emergent visits (E)—predicts 30‐day outcomes following heart failure (HF) hospitalization but is complex to score. A simpler LE index (length of stay and emergent visits) could offer a practical advantage in point‐of‐care risk prediction.

Methods and results

This was a sub‐study of the patient‐centred care transitions in HF (PACT‐HF) multicentre trial. The derivation cohort comprised patients hospitalized for HF, enrolled in the trial, and followed prospectively. External validation was performed retrospectively in a cohort of patients hospitalized for HF. We used log‐binomial regression models with LACE or LE as the predictor and either 30‐day composite all‐cause readmission or death or 30‐day all‐cause readmission as the outcomes, adjusting only for post‐discharge services. There were 1985 patients (mean [SD] age 78.1 [12.1] years) in the derivation cohort and 378 (mean [SD] age 73.1 [13.2] years) in the validation cohort. Increments in the LACE and LE indices were associated with 17% (RR 1.17; 95% CI 1.12, 1.21; C‐statistic 0.64) and 21% (RR 1.21; 95% CI 1.15, 1.26; C‐statistic 0.63) increases, respectively, in 30‐day composite all‐cause readmission or death; and 16% (RR 1.16; 95% CI 1.11, 1.20; C‐statistic 0.64) and 18% (RR 1.18; 95% CI 1.13, 1.24; C‐statistic 0.62) increases, respectively, in 30‐day all‐cause readmission. The LE index provided better risk discrimination for the 30‐day outcomes than did the LACE index in the external validation cohort.

Conclusions

The LE index predicts 30‐day outcomes following HF hospitalization with similar or better performance than the more complex LACE index.
Parvovirus B19 DNA detectable in hearts of patients with dilated cardiomyopathy, but absent or inactive in blood
Authors: Russcher Anne , Verdonschot Job , Molenaar‐de Backer Marijke W.A. , Heymans Stephane R.B. , Kroes Aloys C.M. , Zaaijer Hans L.
Published: May 2021

Aims

Parvovirus B19 (B19V) is often assumed to be a cause of dilated cardiomyopathy (DCM), based on the quantification of B19V DNA in endomyocardial biopsies (EMB). Whether the presence of B19V DNA correlates with active infection is still debated. Application of the enzyme endonuclease to blood samples results in degradation of B19V DNA remnants but leaves viral particles intact, which enables differentiation between active and past infection. In this study, the susceptibility to degradation by endonuclease of B19V DNA in blood was compared between DCM patients and a control group of recent B19V infections.

Methods and results

Twenty blood samples from 20 adult patients with DCM, who previously tested positive for B19V DNA in EMB and/or blood, were tested with B19V PCR before and after application of endonuclease to the samples. Six blood samples tested positive for B19V DNA with a mean viral load of 2.3 × 104 IU/mL. In five samples, B19V DNA became undetectable after endonuclease (100% load reduction); in one sample DNA load showed a 23% log load reduction (viral load before endonuclease: 9.1 × 104 IU/mL; after: 6.5 × 103 IU/mL). Presence of cardiac inflammation did not differ between patients with B19V DNAemia (1/4) and patients without B19V DNAemia (6/14) (P value = 1.0). In all 18 control samples of proven recent B19V infections, DNA remained detectable after application of endonuclease, showing only a mean log load reduction of 2.3% (mean viral load before endonuclease: 8.1 × 1011 IU/mL; after: 8.0 × 1011 IU/mL). Load reduction differed significantly between the DCM group and the control group; indicating the presence of intact viral particles in the control group with proven active infection and the presence of DNA remnants in the DCM group (P value = 0.000).

Conclusion

During recent B19V infection, viral DNA levels in blood were unaffected by endonuclease. In contrast, B19V DNA in blood in patients with DCM became undetectable or strongly reduced after application of endonuclease. Circulating viral DNA in this subset of patients with presumed parvovirus‐associated DCM does not consist of intact viral particles. Viral replicative activity cannot be assumed from demonstrating B19V DNA in cardiac tissue or in blood in DCM patients.
All‐cause mortality predicted by peak oxygen uptake differs depending on spirometry pattern in patients with heart failure and reduced ejection fraction
Authors: Van Iterson Erik H. , Cho Leslie , Tonelli Adriano , Finet J. Emanuel , Laffin Luke J.
Published: May 2021

Aims

In patients with heart failure and reduced ejection fraction (HFrEF), it remains unclear how exacerbated impairments in peak exercise oxygen uptake (V̇O2peak) caused by coexistent obstructive or restrictive ventilatory defects affect mortality risk. We evaluated in patients with HFrEF, whether demonstrating either an obstructive or restrictive‐patterned ventilatory defect on spirometry affects V̇O2peak to yield all‐cause mortality risk predicted by V̇O2peak that is spirometry pattern specific.

Methods and results

We retrospectively analysed resting spirometry and treadmill cardiopulmonary exercise testing data of patients with HFrEF (left ventricular ejection fraction ≤ 40%). The study sample (N = 329) was grouped by spirometry pattern: normal [Group 1: N = 101; forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ≥ 0.70; FVC ≥ 80% predicted], restrictive without airflow obstruction (Group 2: N = 104; FEV1/FVC ≥ 0.70; FVC < 80% predicted), or obstructive (Group 3: N = 124; FEV1/FVC < 0.70). Patients were followed up to 1 year for the endpoint of all‐cause mortality. V̇O2peak was higher in Group 1 versus Groups 2 and 3 (13.4 ± 4.0 vs. 12.1 ± 3.7 and 12.2 ± 3.3 mL/kg/min, respectively; P = 0.014). Over the 1 year follow‐up, n = 9, n = 16, and n = 12 deaths occurred in Groups 1–3, respectively, with corresponding crude survival rates of 88%, 81%, and 92%, respectively (log‐rank; P = 0.352). V̇O2peak was associated with all‐cause mortality (crude hazard ratio = 0.77; P < 0.001). In multivariate analyses, a significant V̇O2peak‐by‐spirometry group interaction yielded 1.99 (95% confidence interval, 1.14–3.46) and 2.43 (95% confidence interval, 1.44–4.11) higher mortality risk associated with V̇O2peak in Group 2 versus Groups 1 and 3, respectively.

Conclusions

Demonstrating a restrictive pattern on spirometry yields the severest mortality risk associated with V̇O2peak. Using spirometry to screen patients with HFrEF for ventilatory defects has a potential role in improving risk stratification based on V̇O2peak.
Clinical phenotypes and prognosis of thyrotoxic heart failure and cardiomyopathy in patients hospitalized for acute heart failure
Authors: Kositanurit Weerapat , Kittipibul Veraprapas , Srichomkwun Panudda , Boonyaratavej Smonporn , Puwanant Sarinya
Published: May 2021

Background

We sought to examine clinical characteristics and outcomes in patients hospitalized for acute heart failure (HF) and thyrotoxicosis.

Methods

Patients with thyrotoxic HF were compared with age and gender‐matched patients hospitalized for acute HF (controls). Thyr‐HF was defined by the Framingham criteria for HF and clinical hyperthyroidism. Thyrotoxic cardiomyopathy was defined as left ventricular ejection fraction (LVEF) < 55%.

Results

Of 11 109 consecutive patients hospitalized for acute HF between 1 January 2002 and 1 January 2017, 92 patients (0.8%) had thyrotoxic HF. Clinical and echocardiographic data were available in 87 patients (age 51 ± 16 years; 74% female), representing the study population. Compared with controls, patients with Thyr‐HF had a smaller body surface area (BSA), a higher LVEF, a lower LV end‐diastolic diameter, a higher tricuspid annular plane systolic excursion (TAPSE), higher blood pressure, higher heart rate, and were more likely to have right‐sided HF at presentation (P < 0.01 for all). The survival rate among patients with thyrotoxic HF was higher than the control group (HR: 4.3; 95% CI: 2.1–9.5). Fifty‐eight percent of patients with thyrotoxic HF had thyrotoxic cardiomyopathy. In multivariate analysis, TAPSE (OR = 46; 95% CI: 1.04–2008.20; P = 0.047) and leukocytosis (OR = 16; 95% CI 1.01–259.39; P = 0.049) correlated with thyrotoxic cardiomyopathy. LV recovery was observed in 69% of these patients.

Conclusions

Thyrotoxic HF was uncommon among patients hospitalized for acute HF. However, after definitive therapy, these patients had a more favourable prognosis than those hospitalized for acute HF without thyrotoxic HF. Clinical phenotypes of thyrotoxic HF include small BSA, middle‐aged female, HF‐pEF, and right‐sided HF. Thyrotoxic cardiomyopathy affected over half of the patients with thyrotoxic HF with a two‐third recovery rate.
Left ventricular geometry transition in hypertensive patients with heart failure with preserved ejection fraction
Authors: Guan Ping , Gu Jun , Song Zhi‐ping , Wang Chang‐qian , Hu Wei , Zhang Jun‐feng
Published: May 2021

Aims

Heart failure with preserved ejection fraction (HFpEF) develops in response to hypertensive left ventricular (LV) hypertrophy and is associated with increased cardiovascular events. Although the progression to systolic heart failure is a known consequence of LV hypertrophy and HFpEF, few data are available on the LV geometry change and frequency of deterioration to systolic dysfunction in this population.

Methods and results

We evaluated the baseline and follow‐up characteristics in 680 patients with LV hypertrophy and HFpEF in this prospective cohort study. The primary endpoint was 5 year all‐cause mortality. The changes of LV geometry and heart failure transition were analysed. Systolic dysfunction [left ventricular ejection fraction (LVEF) < 50%] occurred in 182 patients (26.8%) during a 5 year follow‐up. Patients with LVEF deterioration were associated with a lower survival rate. Beta‐blocker prescription was a protective factor for preserved LVEF. And concentric LV geometry shifted to eccentric hypertrophy was uncommon (10.6%) during a 5 year follow‐up.

Conclusions

A quarter of patients with hypertensive LV hypertrophy and HFpEF progresses to systolic dysfunction during a 5 year follow‐up, which was accompanied by poor clinical outcomes. And beta‐blocker therapy might play a protective role for preserved LVEF in this population.
Impact of diastolic dysfunction on outcome in heart failure patients with mid‐range or reduced ejection fraction
Authors: Liu Dan , Hu Kai , Lau Kolja , Kiwitz Tobias , Robitzkat Katharina , Hammel Clara , Lengenfelder Björn Daniel , Ertl Georg , Frantz Stefan , Nordbeck Peter
Published: May 2021

Aims

The role of diastolic dysfunction (DD) in prognostic evaluation in heart failure (HF) patients with impaired systolic function remains unclear. We investigated the impact of echocardiography‐defined DD on survival in HF patients with mid‐range (HFmrEF, EF 41–49%) and reduced ejection fraction (HFrEF, EF < 40%).

Methods and results

A total of 2018 consecutive hospitalized HF patients were retrospectively included and divided in two groups based on baseline EF: HFmrEF group (n = 951, aged 69 ± 13 years, 74.2% male) and HFrEF group (n = 1067, aged 68 ± 13 years, 76.3% male). Clinical data were collected and analysed. All patients completed ≥1 year clinical follow‐up. The primary endpoint was defined as all‐cause death (including heart transplantation) and cardiovascular (CV)‐related death. All‐cause mortality (30.8% vs. 24.9%, P = 0.003) and CV mortality (19.1% vs. 13.5%, P = 0.001) were significantly higher in the HFrEF group than the HFmrEF group during follow‐up [median 24 (13–36) months]. All‐cause mortality increased in proportion to DD severity (mild, moderate, and severe) in either HFmrEF (17.1%, 25.4%, and 37.0%, P < 0.001) or HFrEF (18.9%, 30.3%, and 39.2%, P < 0.001) patients. The risk of all‐cause mortality [hazard ratio (HR) = 1.347, P = 0.015] and CV mortality (HR = 1.508, P = 0.007) was significantly higher in HFrEF patients with severe DD compared with non‐severe DD after adjustment for identified clinical and echocardiographic covariates. For HFmrEF patients, severe DD was independently associated with increased all‐cause mortality (HR = 1.358, P = 0.046) but not with CV mortality (HR = 1.155, P = 0.469).

Conclusions

Echocardiography‐defined severe DD is independently associated with increased all‐cause mortality in patients with HFmrEF and HFrEF.
Five‐year survival and use of hospital services following ICD and CRT implantation: comparing real‐world data with RCTs
Authors: Bottle Alex , Faitna Puji , Aylin Paul , Cowie Martin R.
Published: May 2021

Aims

Guidelines recommend the use of an implantable cardioverter‐defibrillator (ICD) and/or cardiac resynchronization therapy (CRT) device based on the results of randomized controlled trials (RCTs), typically with selected patients and short follow‐up.

Methods and results

We describe the 5 year survival rate and use of hospital services following ICD and CRT implantation in England from April 2011 to March 2013 using the national hospital administrative database covering emergency department visits, inpatient admissions, and clinic appointments, linked to the national death register. Five‐year survival was 64% after ICD implantation and 58% after CRT implantation, with median survival times of 6.8 and 6.2 years, respectively. Hospital use was high in both device groups, for the 5 years prior and after implantation, peaking around the implantation date. Most hospital activity was not primarily related to heart failure. Healthcare costs were dominated by admissions, but emergency department and clinic activity were both high. Only the CRT group saw total per‐patient costs fall after the index month (implantation), driven by a slight fall in the heart failure admission rate. Patients were typically older than in the trials, but with similar co‐morbidity except for substantially more atrial fibrillation and less dementia. Survival and device complications were similar to the RCTs.

Conclusions

Clinical and cost‐effectiveness assessments of ICD and CRT implantation are supported by real‐world data, although the prevalence of atrial fibrillation remains substantially higher than in the RCTs.
Spot urine sodium in acute heart failure: differences in prognostic value on admission and discharge
Authors: Biegus Jan , Zymliński Robert , Fudim Marat , Testani Jeffrey , Sokolski Mateusz , Marciniak Dominik , Ponikowska Barbara , Guzik Mateusz , Garus Mateusz , Urban Szymon , Ponikowski Piotr
Published: May 2021

Aims

Most studies examined spot urine sodium's (sUNa+) prognostic utility during the early phase of acute heart failure (AHF) hospitalization. In AHF, sodium excretion is related to clinical status; therefore, we investigated the differences in the prognostic information of spot UNa+ throughout the course of hospitalization for AHF (admission vs. discharge).

Methods and results

The study population were AHF patients (n = 172), who survived the index hospitalization. We compared the relationship between early (on admission, at 24 and 48 h) and discharge sUNa+ measurements with post‐discharge study endpoints: composite of 1 year all‐cause mortality and AHF rehospitalization (with time to first event analysis) as well as with each event in separation. There were 49 (28.5%) deaths, 40 (23.3%) AHF rehospitalizations, while the composite endpoint occurred in 69 (40.1%) during 1 year follow‐up. The sUNa+ had prognostic significance for the composite endpoint when assessed on admission, at 24 and at 48 h: hazard ratios (HRs) with 95% confidence intervals (CIs) (per 10 mmol/L) were 0.88 (0.82–0.94); 0.87 (0.81–0.91); 0.90 (0.84–0.96), all P < 0.005. In contrast to early, active decongestion phase, discharge sUNa+ had no prognostic significance HR (95% CI) (per 10 mmol/L): 0.99 (0.93–1.06) P = 0.79 for the composite endpoint, which was independent from the dose of oral furosemide prescribed at that timepoint (average causal mediation effects: −0.38; P = 0.71). Similarly, discharge sUNa+ was neither associated with 1 year mortality HR (95% CI) (per 10 mmol/L): 0.97 (0.89–1.05) P = 0.48 nor with AHF rehospitalizations HR (95% CI) (per 10 mmol/l): 1.03 (0.94–1.12), P = 0.56. The comparison of longitudinal profiles of sUNa+ during hospitalization showed significantly higher values within the early, active decongestive phase in those who did not experience composite endpoint when compared with those who did: admission: 94 ± 34 vs. 76 ± 35; Day 1: 85 ± 36 vs. 65 ± 37; Day 2: 84 ± 37 vs. 67 ± 35, all P < 0.005 (mmol/L), respectively. There was no difference between those groups in discharge sUNa+: 73 ± 35 vs. 70 ± 35 P = 0.82 (mmol/L).

Conclusions

Spot UNa+ assessed at early phase of hospitalization and at discharge have different prognostic significance, which confirms that it should be always interpreted along with clinical context.
The association between heart failure and incident cancer in women: an analysis of the Women's Health Initiative
Authors: Leedy Douglas J. , Reding Kerryn W. , Vasbinder Alexi L. , Anderson Garnet L. , Barac Ana , Wactawski‐Wende Jean , Shadyab Aladdin H. , Eaton Charles B. , Levy Wayne C. , Qi LiHong , Cheng Richard K.
Published: May 2021

Aims

There is conflicting evidence whether heart failure (HF) is a risk factor for incident cancer. Despite population‐based cohorts demonstrating this association, an analysis of the Physician's Health Study found no association in a cohort of mostly healthy males. We investigated the association of HF with incident cancer among a large cohort of post‐menopausal women.

Methods and results

A prospective cohort study of 146 817 post‐menopausal women age 50 to 79 years enrolled in the Women's Health Initiative from 1993–1998, and followed through 2015. The primary exposure was adjudicated incident HF diagnosis, including preserved and reduced ejection fraction in a sub‐cohort. The primary outcome was adjudicated incident total and site‐specific cancers. Hazard ratios were calculated using multivariable‐adjusted Cox proportional hazard regression models. Over a median follow‐up of 8.4 years, 3272 and 17 474 women developed HF and cancer, respectively. HF developed in 235 women prior to cancer. HF was associated with subsequent incident cancer [hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.11–1.48]. Associations were observed for obesity‐related cancers (HR 1.24, 95% CI 1.02–1.51), as well as lung and colorectal cancers (HR 1.58, 95% CI 1.09–2.30 and HR 1.52, 95% CI 1.02–2.27, respectively). HF with preserved ejection fraction (HR 1.34, 95% CI 1.06–1.67), but not HF reduced ejection fraction (HR 0.99, 95% CI 0.74–1.34), was associated with total cancer.

Conclusion

Heart failure was associated with an increase in cancer diagnoses in post‐menopausal women. This association was strongest for lung cancer. Further research is needed to appreciate the underlying mechanisms responsible for this association.
Surgical ablation of the right greater splanchnic nerve for the treatment of heart failure with preserved ejection fraction: first‐in‐human clinical trial
Authors: Málek Filip , Gajewski Piotr , Zymliński Robert , Janczak Dariusz , Chabowski Mariusz , Fudim Marat , Martinca Tomas , Neužil Petr , Biegus Jan , Mates Martin , Krüger Andreas , Skalský Ivo , Bapna Anisha , Engelman Zoar J. , Ponikowski Piotr P.
Published: May 2021

Aims

Inappropriate control of blood volume redistribution may be a mechanism responsible for exercise intolerance in heart failure with preserved ejection fraction (HFpEF). We propose to address this underlying pathophysiology with selective blockade of sympathetic signalling to the splanchnic circulation by surgical ablation of the right greater splanchnic nerve (GSN).

Methods and results

In a single‐arm, prospective, two‐centre trial, 10 patients with HFpEF (50% male, mean age 70 ± 3 years) all with New York Heart Association (NYHA) class III, left ventricular ejection fraction >40%, pulmonary capillary wedge pressure (PCWP) ≥15 mmHg at rest or ≥25 mmHg with supine cycle ergometry, underwent ablation of the right GSN via thoracoscopic surgery. Patients were evaluated at baseline, 1, 3, 6 and 12 months after the procedure. The primary endpoint was a reduction in exercise PCWP at 3 months. There were no adverse events related to the blockade of the nerve during 12‐month follow‐up but three patients had significant peri‐procedural adverse events related to the surgical procedure itself. At 3 months post‐GSN ablation, patients demonstrated a reduction in 20 W exercise PCWP when compared to baseline [−4.5 mmHg (95% confidence interval, CI −14 to −2); P = 0.0059], which carried over to peak exercise [−5 mmHg (95% CI −11 to 0; P = 0.016). At 12 months, improvements were seen in NYHA class [3 (3) vs. 2 (1, 2); P = 0.0039] and quality of life assessed with the Minnesota Living with Heart Failure Questionnaire [60 (51, 71) vs. 22 (16, 27); P = 0.0039].

Conclusion

In this first‐in‐human study, GSN ablation in HFpEF proved to be feasible, with a suggestion of reduced cardiac filling pressure during exercise, improved quality of life and exercise capacity.
Heart failure with preserved ejection fraction according to the HFA‐PEFF score in COVID‐19 patients: clinical correlates and echocardiographic findings
Authors: Hadzibegovic Sara , Lena Alessia , Churchill Timothy W. , Ho Jennifer E. , Potthoff Sophia , Denecke Corinna , Rösnick Lukas , Heim Katrin Moira , Kleinschmidt Malte , Sander Leif Erik , Witzenrath Martin , Suttorp Norbert , Krannich Alexander , Porthun Jan , Friede Tim , Butler Javed , Wilkenshoff Ursula , Pieske Burkert , Landmesser Ulf , Anker Stefan D. , Lewis Gregory D. , Tschöpe Carsten , Anker Markus S.
Published: May 2021

Aims

Viral‐induced cardiac inflammation can induce heart failure with preserved ejection fraction (HFpEF)‐like syndromes. COVID‐19 can lead to myocardial damage and vascular injury. We hypothesised that COVID‐19 patients frequently develop a HFpEF‐like syndrome, and designed this study to explore this.

Methods and results

Cardiac function was assessed in 64 consecutive, hospitalized, and clinically stable COVID‐19 patients from April–November 2020 with left ventricular ejection fraction (LVEF) ≥50% (age 56 ± 19 years, females: 31%, severe COVID‐19 disease: 69%). To investigate likelihood of HFpEF presence, we used the HFA‐PEFF score. A low (0–1 points), intermediate (2–4 points), and high (5–6 points) HFA‐PEFF score was observed in 42%, 33%, and 25% of patients, respectively. In comparison, 64 subjects of similar age, sex, and comorbidity status without COVID‐19 showed these scores in 30%, 66%, and 4%, respectively (between groups: P = 0.0002). High HFA‐PEFF scores were more frequent in COVID‐19 patients than controls (25% vs. 4%, P = 0.001). In COVID‐19 patients, the HFA‐PEFF score significantly correlated with age, estimated glomerular filtration rate, high‐sensitivity troponin T (hsTnT), haemoglobin, QTc interval, LVEF, mitral E/A ratio, and H2FPEF score (all P < 0.05). In multivariate, ordinal regression analyses, higher age and hsTnT were significant predictors of increased HFA‐PEFF scores. Patients with myocardial injury (hsTnT ≥14 ng/L: 31%) vs. patients without myocardial injury, showed higher HFA‐PEFF scores [median 5 (interquartile range 3–6) vs. 1 (0–3), P < 0.001] and more often showed left ventricular diastolic dysfunction (75% vs. 27%, P < 0.001).

Conclusion

Hospitalized COVID‐19 patients frequently show high likelihood of presence of HFpEF that is associated with cardiac structural and functional alterations, and myocardial injury. Detailed cardiac assessments including echocardiographic determination of left ventricular diastolic function and biomarkers should become routine in the care of hospitalized COVID‐19 patients.
Primary results of long‐term outcomes in the MOMENTUM 3 pivotal trial and continued access protocol study phase: a study of 2200 HeartMate 3 left ventricular assist device implants
Authors: Mehra Mandeep R. , Cleveland Joseph C. , Uriel Nir , Cowger Jennifer A. , Hall Shelley , Horstmanshof Douglas , Naka Yoshifumi , Salerno Christopher T. , Chuang Joyce , Williams Christopher , Goldstein Daniel J. ,    on behalf of the MOMENTUM 3 Investigators
Published: May 2021

Aim

The MOMENTUM 3 pivotal trial established superiority of the HeartMate 3 (HM3) left ventricular assist device (LVAD), a fully magnetically levitated centrifugal‐flow pump, over the HeartMate II axial‐flow pump. We now evaluate HM3 LVAD outcomes in a single‐arm prospective continuous access protocol (CAP) post‐pivotal trial study.

Methods and results

We enrolled 2200 HM3 implanted patients (515 pivotal trial and 1685 CAP patients) and compared outcomes including survival free of disabling stroke or reoperation to replace or remove a malfunctioning device (primary composite endpoint), overall survival and major adverse events at 2 years. The 2‐year primary endpoint [76.7% vs. 74.8%; adjusted hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.71–1.08, P = 0.21] and overall survival (81.2% vs. 79.0%) were similar among CAP and pivotal cohorts despite sicker patients (more intra‐aortic balloon pump use and INTERMACS profile 1) in CAP who were more often intended for destination therapy. Survival was similar between the CAP and pivotal trial in transplant ineligible patients (79.1% vs. 76.7%; adjusted HR 0.89, 95% CI 0.68–1.16, P = 0.38). In a pooled analysis, the 2‐year primary endpoint was similar between INTERMACS profiles 1–2 (‘unstable’ advanced heart failure), profile 3 (‘stable’ on inotropic therapy), and profiles 4–7 (‘stable’ ambulatory advanced heart failure) (75.7% vs. 77.6% vs. 72.9%, respectively). The net burden of adverse events was lower in CAP (adjusted rate ratio 0.93, 95% CI 0.88–0.98, P = 0.006), with consequent decrease in hospitalization.

Conclusions

The primary results of accumulating HM3 LVAD experience suggest a lower adverse event burden and similar survival compared to the pivotal MOMENTUM 3 trial.
The Design of Gold Decorated Iron Borates (Fe3BO6 and FeBO3) for Photothermal Therapy and Boron Carriers
Authors: Icten Okan
Published: May 2021

Cancer remains one of the serious diseases that threaten health, as treatment methods cannot meet the practical needs at the desired level. Therefore, developing new materials that can be used in cancer treatment is an essential effort. The purpose of this study was to develop new materials for boron neutron capture therapy (BNCT) as boron carriers and for photothermal therapy (PTT). Hence, iron borates were prepared with different morphologies and then coated with polydopamine (PDA) to increase the solubility and biocompatibility and also to contribute to the reduction in gold particles. Lastly, gold nanoparticles were deposited on the surface of iron borates, and the photothermal performance of the gold‐decorated and PDA‐coated iron borates (Fe3BO6@PDA−Au and FeBO3@PDA−Au) was investigated under 808 nm NIR laser. After 900 s irradiation, the temperatures of the dispersions of Fe3BO6@PDA−Au and FeBO3@PDA−Au nanoparticles reached 45.8 and 43.2 °C, respectively. Additionally, the approximate numbers of boron atoms per milligram of Fe3BO6@PDA−Au and FeBO3@PDA−Au nanoparticles were calculated to be 1.23×1018 B mg−1 and 2.79×1018 B mg−1, respectively. In addition to PTT, the functional Fe3BO6@PDA−Au and FeBO3@PDA−Au nanoparticles introduced herein could be helpful in BNCT applications.