2 research outputs found
Effects of Atrial Fibrillation on the Human Ventricle
Rationale:
Atrial fibrillation (AF) and heart failure often coexist, but their interaction is poorly understood. Clinical data indicate that the arrhythmic component of AF may contribute to left ventricular (LV) dysfunction.
Objective:
This study investigates the effects and molecular mechanisms of AF on the human LV.
Methods and Results:
Ventricular myocardium from patients with aortic stenosis and preserved LV function with sinus rhythm or rate-controlled AF was studied. LV myocardium from patients with sinus rhythm and patients with AF showed no differences in fibrosis. In functional studies, systolic Ca2+ transient amplitude of LV cardiomyocytes was reduced in patients with AF, while diastolic Ca2+ levels and Ca2+ transient kinetics were not statistically different. These results were confirmed in LV cardiomyocytes from nonfailing donors with sinus rhythm or AF. Moreover, normofrequent AF was simulated in vitro using arrhythmic or rhythmic pacing (both at 60 bpm). After 24 hours of AF-simulation, human LV cardiomyocytes from nonfailing donors showed an impaired Ca2+ transient amplitude. For a standardized investigation of AF-simulation, human iPSC-cardiomyocytes were tested. Seven days of AF-simulation caused reduced systolic Ca2+ transient amplitude and sarcoplasmic reticulum Ca2+ load likely because of an increased diastolic sarcoplasmic reticulum Ca2+ leak. Moreover, cytosolic Na+ concentration was elevated and action potential duration was prolonged after AF-simulation. We detected an increased late Na+ current as a potential trigger for the detrimentally altered Ca2+/Na+-interplay. Mechanistically, reactive oxygen species were higher in the LV of patients with AF. CaMKII (Ca2+/calmodulin-dependent protein kinase IIδc) was found to be more oxidized at Met281/282 in the LV of patients with AF leading to an increased CaMKII activity and consequent increased RyR2 phosphorylation. CaMKII inhibition and ROS scavenging ameliorated impaired systolic Ca2+ handling after AF-simulation.
Conclusions:
AF causes distinct functional and molecular remodeling of the human LV. This translational study provides the first mechanistic characterization and the potential negative impact of AF in the absence of tachycardia on the human ventricle
Same but Different? Comparing the Epidemiology, Treatments and Outcomes of COVID-19 and Non-COVID-19 ARDS Cases in Germany Using a Sample of Claims Data from 2021 and 2019
Background: Acute respiratory distress syndrome (ARDS) is a severe lung condition that can be caused by a variety of underlying illnesses. Due to SARS-CoV-2, the number of cases with ARDS has increased worldwide, making it essential to compare this form of acute respiratory failure with classical causes of ARDS. While there have been several studies investigating the differences between COVID-19 and non-COVID-19 ARDS in early stages of the pandemic, little is known about the differences in later phases, especially in Germany. Aim: The aim of this study is to characterize and compare the comorbidities, treatments, adverse events, and outcomes of COVID-19-associated ARDS and non-COVID-19 ARDS using a representative sample of German health claims data from the years 2019 and 2021. Methods: We compare percentages and median values of the quantities of interest from the COVID-19 and non-COVID-19 ARDS group, with p-values calculated after conducting Pearson’s chi-squared test or the Wilcoxon rank sum test. We also run logistic regressions to access the effect of comorbidities on mortality for COVID-19 ARDS and non-COVID-19 ARDS. Results: Despite many similarities, we find that that there are some remarkable differences between COVID-19 and non-COVID-19 ARDS cases in Germany. Most importantly, COVID-19 ARDS cases display fewer comorbidities and adverse events, and are more often treated with non-invasive ventilation and nasal high-flow therapy. Conclusions: This study highlights the importance of comprehending the contrasting epidemiological features and clinical outcomes of COVID-19 and non-COVID-19 ARDS. This understanding can aid in clinical decision making and guide future research initiatives aimed at enhancing the management of patients afflicted with this severe condition