Mathias Kaspar

Prognostic potential of midregional pro-adrenomedullin following decompensation for systolic heart failure: comparison with cardiac natriuretic peptides

Whereas guidelines recommend the routine use of natriuretic peptides (NPs) in heart failure (HF) care, the clinical relevance and prognostic potential of midregional pro‐adrenomedullin (MR‐proADM) is less well established. We aimed to compare the prognostic potential of MR‐proADM after acute decompensation for systolic HF with that of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) and midregional pro‐atrial NP (MR‐proANP), to investigate the significance of high/rising MR‐proADM, and to evaluate the incremental prognostic yield of repeat measurements.

Inositol 1,4,5-trisphosphate-mediated sarcoplasmic reticulum–mitochondrial crosstalk influences adenosine triphosphate production via mitochondrial Ca2+ uptake through the mitochondrial ryanodine receptor in cardiac myocytes

AIMS Elevated levels of inositol 1,4,5-trisphosphate (IP3) in adult cardiac myocytes are typically associated with the development of cardiac hypertrophy, arrhythmias, and heart failure. IP3 enhances intracellular Ca(2+ )release via IP3 receptors (IP3Rs) located at the sarcoplasmic reticulum (SR). We aimed to determine whether IP3-induced Ca(2+ )release affects mitochondrial function and determine the underlying mechanisms. METHODS AND RESULTS We compared the effects of IP3Rs- and ryanodine receptors (RyRs)-mediated cytosolic Ca(2+ )elevation achieved by endothelin-1 (ET-1) and isoproterenol (ISO) stimulation, respectively, on mitochondrial Ca(2+ )uptake and adenosine triphosphate (ATP) generation. Both ET-1 and isoproterenol induced an increase in mitochondrial Ca(2+ )(Ca(2 +) m) but only ET-1 led to an increase in ATP concentration. ET-1-induced effects were prevented by cell treatment with the IP3 antagonist 2-aminoethoxydiphenyl borate and absent in myocytes from transgenic mice expressing an IP3 chelating protein (IP3 sponge). Furthermore, ET-1-induced mitochondrial Ca(2+) uptake was insensitive to the mitochondrial Ca(2+ )uniporter inhibitor Ru360, however was attenuated by RyRs type 1 inhibitor dantrolene. Using real-time polymerase chain reaction, we detected the presence of all three isoforms of IP3Rs and RyRs in murine ventricular myocytes with a dominant presence of type 2 isoform for both receptors. CONCLUSIONS Stimulation of IP3Rs with ET-1 induces Ca(2+ )release from the SR which is tunnelled to mitochondria via mitochondrial RyR leading to stimulation of mitochondrial ATP production.

A functional variant of the neuropeptide S receptor-1 gene modulates clinical outcomes and healthcare utilization in patients with systolic heart failure: results from the Interdisciplinary Network Heart Failure (INH) Study: NPSR1 polymorphism and outcomes in HF

Psychopathologies may occur in heart failure (HF) and can be associated with adverse outcomes. Amongst neuropeptide S receptor gene functional sequence variants, the T‐allele [asparagine(107)isoleucine, NPSR1 rs324981] has been identified as a risk factor for increased anxiety/overinterpretation of bodily symptoms. We investigated all‐cause death and re‐hospitalization (composite primary endpoint, CPEP) and healthcare utilization in patients hospitalized for decompensated systolic HF with the TT vs. the AT/AA genotype.

Data Linkage from Clinical to Study Databases via an R Data Warehouse User Interface. Experiences from a Large Clinical Follow-up Study.

BACKGROUND Data that needs to be documented for clinical studies has often been acquired and documented in clinical routine. Usually this data is manually transferred to Case Report Forms (CRF) and/or directly into an electronic data capture (EDC) system. OBJECTIVES To enhance the documentation process of a large clinical follow-up study targeting patients admitted for acutely decompensated heart failure by accessing the data created during routine and study visits from a hospital information system (HIS) and by transferring it via a data warehouse (DWH) into the studys EDC system. METHODS This project is based on the clinical DWH developed at the University of Würzburg. The DWH was extended by several new data domains including data created by the study team itself. An R user interface was developed for the DWH that allows to access its source data in all its detail, to transform data as comprehensively as possible by R into study-specific variables and to support the creation of data and catalog tables. RESULTS A data flow was established that starts with labeling patients as study patients within the HIS and proceeds with updating the DWH with this label and further data domains at a daily rate. Several study-specific variables were defined using the implemented R user interface of the DWH. This system was then used to export these variables as data tables ready for import into our EDC system. The data tables were then used to initialize the first 296 patients within the EDC system by pseudonym, visit and data values. Afterwards, these records were filled with clinical data on heart failure, vital parameters and time spent on selected wards. CONCLUSIONS This solution focuses on the comprehensive access and transformation of data for a DWH-EDC system linkage. Using this system in a large clinical study has demonstrated the feasibility of this approach for a study with a complex visit schedule.

Underestimated prevalence of heart failure in hospital inpatients: a comparison of ICD codes and discharge letter information

BackgroundHeart failure is the predominant cause of hospitalization and amongst the leading causes of death in Germany. However, accurate estimates of prevalence and incidence are lacking. Reported figures originating from different information sources are compromised by factors like economic reasons or documentation quality.MethodsWe implemented a clinical data warehouse that integrates various information sources (structured parameters, plain text, data extracted by natural language processing) and enables reliable approximations to the real number of heart failure patients. Performance of ICD-based diagnosis in detecting heart failure was compared across the years 2000–2015 with (a) advanced definitions based on algorithms that integrate various sources of the hospital information system, and (b) a physician-based reference standard.ResultsApplying these methods for detecting heart failure in inpatients revealed that relying on ICD codes resulted in a marked underestimation of the true prevalence of heart failure, ranging from 44% in the validation dataset to 55% (single year) and 31% (all years) in the overall analysis. Percentages changed over the years, indicating secular changes in coding practice and efficiency. Performance was markedly improved using search and permutation algorithms from the initial expert-specified query (F1 score of 81%) to the computer-optimized query (F1 score of 86%) or, alternatively, optimizing precision or sensitivity depending on the search objective.ConclusionsEstimating prevalence of heart failure using ICD codes as the sole data source yielded unreliable results. Diagnostic accuracy was markedly improved using dedicated search algorithms. Our approach may be transferred to other hospital information systems.

Ad Hoc Information Extraction for Clinical Data Warehouses

Summary Background: Clinical Data Warehouses (CDW) reuse Electronic health records (EHR) to make their data retrievable for research purposes or patient recruitment for clinical trials. However, much information are hidden in unstructured data like discharge letters. They can be preprocessed and converted to structured data via information extraction (IE), which is unfortunately a laborious task and therefore usually not available for most of the text data in CDW. Objectives: The goal of our work is to provide an ad hoc IE service that allows users to query text data ad hoc in a manner similar to querying structured data in a CDW. While search engines just return text snippets, our systems also returns frequencies (e.g. how many patients exist with “heart failure” including textual synonyms or how many patients have an LVEF < 45) based on the content of discharge letters or textual reports for special investigations like heart echo. Three subtasks are addressed: (1) To recognize and to exclude negations and their scopes, (2) to extract concepts, i.e. Boolean values and (3) to extract numerical values. Methods: We implemented an extended version of the NegEx-algorithm for German texts that detects negations and determines their scope. Furthermore, our document oriented CDW PaDaWaN was extended with query functions, e.g. context sensitive queries and regex queries, and an extraction mode for computing the frequencies for Boolean and numerical values. Results: Evaluations in chest X-ray reports and in discharge letters showed high F1-scores for the three subtasks: Detection of negated concepts in chest X-ray reports with an F1-score of 0.99 and in discharge letters with 0.97; of Boolean values in chest X-ray reports about 0.99, and of numerical values in chest X-ray reports and discharge letters also around 0.99 with the exception of the concept age. Discussion: The advantages of an ad hoc IE over a standard IE are the low development effort (just entering the concept with its variants), the promptness of the results and the adaptability by the user to his or her particular question. Disadvantage are usually lower accuracy and confidence. This ad hoc information extraction approach is novel and exceeds existing systems: Roogle [ 1 ] extracts predefined concepts from texts at preprocessing and makes them retrievable at runtime. Dr. Warehouse [ 2 ] applies negation detection and indexes the produced subtexts which include affirmed findings. Our approach combines negation detection and the extraction of concepts. But the extraction does not take place during preprocessing, but at runtime. That provides an ad hoc, dynamic, interactive and adjustable information extraction of random concepts and even their values on the fly at runtime. Conclusions: We developed an ad hoc information extraction query feature for Boolean and numerical values within a CDW with high recall and precision based on a pipeline that detects and removes negations and their scope in clinical texts.