Mechanical assist in cardiac arrest: Optimising circulatory support. Experimental studies.

Introduction: Mechanical circulatory support (MCS) may be useful in cardiac arrest (CA), both in- and out- of hospital. However, efficacy and survival benefit has been difficult to evaluate compared to standard cardiopulmonary resuscitation. In three experimental studies we aimed to assess different modes of MCS during CA in providing adequate organ perfusion and systemic circulation and identify predictors of sustainable post-CA heart function. Different theoretical assumptions were the background for analysis in the three study protocols performed as acute experiments in anaesthetized pigs: Paper I: A major limitation to the effectiveness of a LVAD alone during CA is the lack of left ventricular (LV) filling due to minimal pulmonary circulation. We therefore wanted to assess if the combination of a left- and right ventricular assist device (BIVAD/BiPella) was beneficial as circulatory support versus a LVAD alone. Paper II: ECMO has the potential to replace systemic circulation during CA. However, concerns have been voiced regarding retrograde flow-delivery and effect on the myocardium during circulatory collapse. Based on results from Paper I we optimized BiPella support aiming to improve and maintain acceptable coronary perfusion pressure, believing this could potentially rectify the poor outcome of BIVAD/BiPella in Paper I if successful. Thus, in Paper II we compared the efficacy of balanced biventricular circulatory assist with extracorporeal membrane oxygenation (ECMO). Paper III: Pressure build-up in the left ventricle during cardiac arrest may be detrimental during extracorporeal cardiopulmonary resuscitation (ECPR) as indicated in Paper II. Therefore, we wished to investigate if unloading (venting) the left ventricle using add-on LVAD could be of benefit. However, the ideal flow-contributions of each assist device when combining LVAD and ECMO during ECPR in is not known. We therefore wanted to compare ECMO with standard or reduced flow and add-on LVAD versus ECMO alone. Finally, we wished to assess the contribution of add-on LVAD regarding pulmonary flow. Materials and methods: The animal experiments were performed at the Vivarium, University of Bergen, and protocols were approved by the Norwegian Animal Research Authority or by the Norwegian Food Safety Authority. Paper I and II were performed with percutaneous techniques. The final experiment was an open chest model. All protocols followed a similar timeline: 1. Anaesthesia and instrumentation of the pig. 2. Baseline evaluation. 3. Induction of CA by application of a 9V DC battery to the myocardium. 4. Immediate initiation of mechanical circulatory support (MCS). 5. Three attempts of cardioversion at the end of the CA period. 6. If successful return of spontaneous circulation (ROSC) was achieved, unsupported observation (Paper II and Paper III). Comparisons between intervention groups: 1. Haemodynamics (during and after CA). 2. Organ tissue blood flow rate (organ perfusion) and device output as calculated from fluorescent microspheres. 3. Arterial blood gases and biomarkers. 4. ROSC. 5. Sustained cardiac function post-ROSC (Paper II and Paper III). In Paper I, twenty animals were randomized in two groups receiving circulatory support either by the Impella CP alone (LVAD) or in combination with the Impella RP (BIVAD/BiPella) during 30 minutes of CA. In Paper II, twenty pigs were randomized to receive MCS either by BiPella or by extracorporeal membrane oxygenation (ECMO) during 40 minutes of CA. If ROSC was successful, animals were observed for 60 minutes unsupported. In Paper III, twenty-four animals were randomized in three groups. Extracorporeal cardiopulmonary resuscitation (ECPR) in Group 1 was provided by ECMO with standard-flow and add-on Impella CP. In Group 2: ECMO with reduced flow combined with Impella CP. In Group 3, animals were supported by standard-flow ECMO alone. ECPR lasted for 60 minutes. If ROSC was successful, 180 minutes unsupported observation followed. Results: Paper I demonstrated that BIVAD/BiPella provides superior circulatory support and perfusion for peripheral organs (including the brain) related to higher LVAD output and increased central aortic pressure compared to LVAD alone. However, myocardial perfusion was related to the pressure difference between mean aortic pressure and mean left ventricular pressure during cardiac arrest. Myocardial perfusion was inferior with BiPella resulting in significantly fewer ROSC (5/10 vs 10/10, p = 0.033) despite significantly higher etCO2 (p = 0.029). Paper II showed that balancing RVAD and LVAD to ensure acceptable coronary perfusion pressure and concomitant LVAD output was feasible, also sustaining vital organ perfusion. However, ECMO provided a more optimal systemic circulatory support. Device output and mean aortic pressure were increased with subsequent improved peripheral tissue perfusion reflected by reduction of s-lactate. In animals where sufficient myocardial perfusion pressure (mean aortic pressure – mean LV pressure > 10-15 mmHg) could not be achieved, perfusion (ml/min/g) was reduced in the subendo- and midmyocardium, averaging 0.59 ± 0.05 vs. 0.31 ± 0.07, (p = 0.005) and 0.91 ± 0.06 vs 0.65 ± 0.15 (p = 0.085), but not in the subepicardium (1.02 ± 0.07 vs 0.86 ± 0.17, p = 0.30) irrespective of group. These subjects also had inferior post-ROSC cardiac function. Paper III showed that add-on LVAD improved haemodynamics compared with ECMO alone during refractory CA. Add-on LVAD could not substitute a reduced ECMO-flow. Three animals with reduced ECMO flow and adjunctive Impella support did not achieve ROSC. With ECMO alone, ROSC was obtained in all animals. However, 4/8 died post-ROSC due to development of cardiogenic shock. In the remaining 21 animals, 17 animals had sustained cardiac function at study termination 3 h after ROSC. Animals without sustained cardiac function (7/24) had reduced mAP (p < 0.001), CPP (p = 0.002) and mPAf (p = 0.004) during CA and ECPR. Conclusions: Paper I: Biventricular support during cardiac arrest was associated with high intraventricular pressure in the left ventricle resulting in decreased myocardial perfusion pressure, reduced myocardial tissue blood flow rate and subsequent reduction in ROSC. Paper II: Myocardial perfusion and sustained cardiac function were related to myocardial perfusion pressure during VF irrespective of MCS (ECMO and balanced biventricular support). Balanced biventricular support maintained lower intraventricular pressure compared to ECMO. Paper III: Add-on LVAD improved haemodynamics compared to ECMO alone. An add-on Impella could not substitute a reduction in ECMO flow. Increased mean aortic pressure, myocardial perfusion pressure and mean pulmonary artery flow were related to sustained cardiac function and ROSC.Doktorgradsavhandlin

Anxiety and depression in patients aged 80 years and older following aortic valve therapy. A six‑month follow‑up study

Background Little is known about mental health following advanced cardiac procedures in the oldest patients. Aims To study changes in anxiety and depression from baseline to one- and six-month follow-up in older patients following transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR). Methods Prospective cohort study of patients ≥ 80 years undergoing elective TAVI or SAVR in a tertiary university hospital. Anxiety and depression were assessed with the Hospital Anxiety and Depression Scale. Differences between TAVI/SAVR were analyzed using Welch’s t test or chi-squared. Changes over time and group differences were established with longitudinal models using generalized least squares. Results In 143 patients (83.5 ± 2.7 years), 46% (n = 65) received TAVI. Anxiety was identified in 11% of TAVI patients at baseline. One- and six-months later, percentages were 8% and 9%. In SAVR patients, 18% had baseline scores indicating anxiety. One and six-months later, percentages were 11% and 9%. Depression was identified in 15% of TAVI patients. One- and six-months later, percentages were 11% and 17%. At baseline, 11% of SAVR patients had scores indicating depression. One- and six-months after SAVR, percentages were 15% and 12%. Longitudinal analyses showed reductions (P < 0.001) in anxiety from baseline to one-month, and stable scores between one- and six-months for both treatment groups. There was no change over time for depression among treatment groups (P = 0.21). Discussion and conclusions SAVR or TAVI in patients ≥ 80 years was associated with anxiety reduction between baseline and follow-up. For depression, there was no evidence of change over time in either treatment group.publishedVersio

On twisted Fourier analysis and convergence of Fourier series on discrete groups

We study norm convergence and summability of Fourier series in the setting of reduced twisted group $C^*$-algebras of discrete groups. For amenable groups, F{\o}lner nets give the key to Fej\'er summation. We show that Abel-Poisson summation holds for a large class of groups, including e.g. all Coxeter groups and all Gromov hyperbolic groups. As a tool in our presentation, we introduce notions of polynomial and subexponential H-growth for countable groups w.r.t. proper scale functions, usually chosen as length functions. These coincide with the classical notions of growth in the case of amenable groups.Comment: 35 pages; abridged, revised and update

Baseline frailty status and outcomes important for shared decision-making in older adults receiving transcatheter aortic valve implantation, a prospective observational study.

AIMS The objective of this study was to examine baseline frailty status (including cognitive deficits) and important clinical outcomes, to inform shared decision-making in older adults receiving transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS We conducted a prospective, observational study of 82 TAVI patients, recruited 2013 to 2015, with 2-year follow-up. Mean age was 83 years (standard deviation (SD) 4.7). Eighteen percent of the patients were frail, as assessed with an 8-item frailty scale. Fifteen patients (18%) had a Mini-Mental Status Examination (MMSE) score below 24 points at baseline, indicating cognitive impairment or dementia and five patients had an MMSE below 20 points. Mean New York Heart Association (NYHA) class at baseline and 6 months was 2.5 (SD 0.6) and 1.4 (SD 0.6), (p < 0.001). There was no change in mean Nottingham Extended Activities of Daily Living (NEADL) scale between baseline and 6 months, 54.2 (SD 11.5) and 54.5 (SD 10.3) points, respectively, mean difference 0.3 (p = 0.7). At 2 years, six patients (7%) had died, four (5%, n = 79) lived in a nursing home, four (5%) suffered from disabling stroke, and six (7%) contracted infective endocarditis. CONCLUSIONS TAVI patients had improvement in symptoms and maintenance of activity of daily living at 6 months. They had low mortality and most patients lived in their own home 2 years after TAVI. Complications like death, stroke, and endocarditis occurred. Some patients had cognitive impairment before the procedure which might influence decision-making. Our findings may be used to develop pre-TAVI decision aids

Calling on a million minds for community annotation in WikiProteins.

WikiProteins enables community annotation in a Wiki-based system. Extracts of major data sources have been fused into an editable environment that links out to the original sources. Data from community edits create automatic copies of the original data. Semantic technology captures concepts co-occurring in one sentence and thus potential factual statements. In addition, indirect associations between concepts have been calculated. We call on a 'million minds' to annotate a 'million concepts' and to collect facts from the literature with the reward of collaborative knowledge discovery. The system is available for beta testing at http://www.wikiprofessional.org.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

The diversity of population responses to environmental change

This is the final version. Available from Wiley via the DOI in this record.Data available from the Dryad Digital Repository: https:// doi.org/10.5061/dryad.d5f54s7The current extinction and climate change crises pressure us to predict population dynamics with ever-greater accuracy. Although predictions rest on the well-advanced theory of age-structured populations, two key issues remain poorly explored. Specifically, how the age-dependency in demographic rates and the year-to-year interactions between survival and fecundity affect stochastic population growth rates. We use inference, simulations and mathematical derivations to explore how environmental perturbations determine population growth rates for populations with different age-specific demographic rates and when ages are reduced to stages. We find that stage- vs. age-based models can produce markedly divergent stochastic population growth rates. The differences are most pronounced when there are survival-fecundity-trade-offs, which reduce the variance in the population growth rate. Finally, the expected value and variance of the stochastic growth rates of populations with different age-specific demographic rates can diverge to the extent that, while some populations may thrive, others will inevitably go extinct.Max Planck Society, Marie Curie FellowshipERCGerman Research FoundationSwiss National Science FoundationNational Science FoundationNational Institute of AgingRamon y Cajal Research GrantWenner-Gren FoundationLeakey FoundationNational Geographic SocietyZoological Society of San DiegoUniversity of PennsylvaniaArgentinean National Council of Researc

The FAIR Guiding Principles for scientific data management and stewardship

There is an urgent need to improve the infrastructure supporting the reuse of scholarly data. A diverse set of stakeholders—representing academia, industry, funding agencies, and scholarly publishers—have come together to design and jointly endorse a concise and measureable set of principles that we refer to as the FAIR Data Principles. The intent is that these may act as a guideline for those wishing to enhance the reusability of their data holdings. Distinct from peer initiatives that focus on the human scholar, the FAIR Principles put specific emphasis on enhancing the ability of machines to automatically find and use the data, in addition to supporting its reuse by individuals. This Comment is the first formal publication of the FAIR Principles, and includes the rationale behind them, and some exemplar implementations in the community

Impact of COVID-19 Pandemic on TAVR Activity: A Worldwide Registry

Background: The COVID-19 pandemic had a considerable impact on the provision of structural heart intervention worldwide. Our objectives were: 1) to assess the impact of the COVID-19 pandemic on transcatheter aortic valve replacement (TAVR) activity globally; and 2) to determine the differences in the impact according to geographic region and the demographic, development, and economic status of diverse international health care systems. Methods: We developed a multinational registry of global TAVR activity and invited individual TAVR sites to submit TAVR implant data before and during the COVID-19 pandemic. Specifically, the number of TAVR procedures performed monthly from January 2019 to December 2021 was collected. The adaptive measures to maintain TAVR activity by each site were recorded, as was a variety of indices relating to type of health care system and national economic indices. The primary subject of interest was the impact on TAVR activity during each of the pandemic waves (2020 and 2021) compared with the same period pre–COVID-19 (2019). Results: Data were received from 130 centers from 61 countries, with 14 subcontinents and 5 continents participating in the study. Overall, TAVR activity increased by 16.7% (2,337 procedures) between 2018 and 2019 (ie, before the pandemic), but between 2019 and 2020 (ie, first year of the pandemic), there was no significant growth (–0.1%; –10 procedures). In contrast, activity again increased by 18.9% (3,085 procedures) between 2020 and 2021 (ie, second year of the pandemic). During the first pandemic wave, there was a reduction of 18.9% (945 procedures) in TAVR activity among participating sites, while during the second and third waves, there was an increase of 6.7% (489 procedures) and 15.9% (1,042 procedures), respectively. Further analysis and results of this study are ongoing and will be available at the time of the congress. Conclusion: The COVID-19 pandemic initially led to a reduction in the number of patients undergoing TAVR worldwide, although health care systems subsequently adapted, and the number of TAVR recipients continued to grow in subsequent COVID-19 pandemic waves. Categories: STRUCTURAL: Valvular Disease: Aorti

Genome-wide association study of thyroid-stimulating hormone highlights new genes, pathways and associations with thyroid disease

Thyroid hormones play a critical role in regulation of multiple physiological functions and thyroid dysfunction is associated with substantial morbidity. Here, we use electronic health records to undertake a genome-wide association study of thyroid-stimulating hormone (TSH) levels, with a total sample size of 247,107. We identify 158 novel genetic associations, more than doubling the number of known associations with TSH, and implicate 112 putative causal genes, of which 76 are not previously implicated. A polygenic score for TSH is associated with TSH levels in African, South Asian, East Asian, Middle Eastern and admixed American ancestries, and associated with hypothyroidism and other thyroid disease in South Asians. In Europeans, the TSH polygenic score is associated with thyroid disease, including thyroid cancer and age-of-onset of hypothyroidism and hyperthyroidism. We develop pathway-specific genetic risk scores for TSH levels and use these in phenome-wide association studies to identify potential consequences of pathway perturbation. Together, these findings demonstrate the potential utility of genetic associations to inform future therapeutics and risk prediction for thyroid diseases