Publications by authors named "Karsten Keller"

100 Publications

Risk Factors for Pulmonary Embolism in Patients with Paralysis and Deep Venous Thrombosis.

J Clin Med 2021 Nov 19;10(22). Epub 2021 Nov 19.

Department of Cardiology, Cardiology I, University Medical Center Mainz (Johannes Gutenberg-University Mainz), 55131 Mainz, Germany.

Background: Venous thromboembolism is a frequent complication and an important cause of death in patients with paralysis. We aimed to investigate predictors of pulmonary embolism (PE) and the impact of PE on the survival of patients with paralysis in comparison to those with deep venous thrombosis or thrombophlebitis (DVT).

Methods: Patients were selected by screening the German nationwide inpatient sample (2005-2017) for paralysis, and were stratified for venous thromboembolism (VTE) and the VTE-sub-entity PE (ICD-code I26). Impact of PE on mortality and predictors for PE were analyzed.

Results: Overall, 7,873,769 hospitalizations of patients with paralysis were recorded in Germany 2005-2017, of whom 1.6% had VTE and 7.0% died. While annual hospitalizations increased (2005: 520,357 to 2017: 663,998) (β 12,421 (95% CI 10,807 to 14,034), < 0.001), in-hospital mortality decreased from 7.5% to 6.7% (β -0.08% (95% CI -0.10% to -0.06%), < 0.001). When focusing on 82,558 patients with paralysis hospitalized due to VTE (51.8% females; 58.3% aged ≥ 70 years) in 2005-2017, in-hospital mortality was significantly higher in patients with paralysis and PE than in those with DVT only (23.8% vs. 6.3%, < 0.001). Cancer (OR 2.18 (95% CI 2.09-2.27), < 0.001), heart failure (OR 1.83 (95% CI 1.76-1.91), < 0.001), COPD (OR 1.63 (95% CI 1.53-1.72), < 0.001) and obesity (OR 1.42 (95% CI 1.35-1.50), < 0.001) were associated with PE. PE (OR 4.28 (95% CI 4.07-4.50), < 0.001) was a strong predictor of in-hospital mortality.

Conclusions: In Germany, annual hospitalizations of patients with paralysis increased in 2005-2017, in whom VTE and especially PE substantially affected in-hospital mortality. Cancer, heart failure, COPD, obesity and acute paraplegia were risk factors of PE.
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http://dx.doi.org/10.3390/jcm10225412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618323PMC
November 2021

Entropy Measures for Data Analysis II: Theory, Algorithms and Applications.

Authors:
Karsten Keller

Entropy (Basel) 2021 Nov 12;23(11). Epub 2021 Nov 12.

Institut für Mathematik, Universität zu Lübeck, D-23562 Lübeck, Germany.

Entropies and entropy-like quantities are playing an increasing role in modern non-linear data analysis [...].
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http://dx.doi.org/10.3390/e23111496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619551PMC
November 2021

Right atrium size in the general population.

Sci Rep 2021 Nov 18;11(1):22523. Epub 2021 Nov 18.

Department of Cardiology, Cardiology I, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany.

Echocardiography is the most common routine cardiac imaging method. Nevertheless, only few data about sex-specific reference limits for right atrium (RA) dimensions are available. Transthoracic echocardiographic RA measurements were studied in 9511 participants of the Gutenberg-Health-Study. A reference sample of 1942 cardiovascular healthy subjects without chronic obstructive pulmonary disease was defined. We assessed RA dimensions and sex-specific reference limits were defined using the 95th percentile of the reference sample. Results showed sex-specific differences with larger RA dimensions in men that were attenuated by standardization for body-height. RA-volume was 20.2 ml/m in women (5th-95th: 12.7-30.4 ml/m) and 26.1 ml/m in men (5th-95th: 16.0-40.5 ml/m). Multivariable regressions identified body-mass-index (BMI), coronary artery disease (CAD), chronic heart failure (CHF) and atrial fibrillation (AF) as independent key correlates of RA-volume in both sexes. All-cause mortality after median follow-up-period of 10.7 (9.81/11.6) years was higher in individuals who had RA volume/height outside the 95% reference limit (HR 1.70 [95%CI 1.29-2.23], P = 0.00014)). Based on a large community-based sample, we present sex-specific reference-values for RA dimensions normalized for height. RA-volume varies with BMI, CHF, CAD and AF in both sexes. Individuals with RA-volume outside the reference limit had a 1.7-fold higher mortality than those within reference limits.
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http://dx.doi.org/10.1038/s41598-021-01968-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602329PMC
November 2021

Diabetes mellitus and its impact on mortality rate and outcome in pulmonary embolism.

J Diabetes Investig 2021 Nov 14. Epub 2021 Nov 14.

Department of Cardiology, Cardiology I, University Medical Center Mainz (Johannes Gutenberg-University Mainz), Mainz, Germany.

Aims/introduction: In patients with pulmonary embolism (PE), the impact of diabetes mellitus on patient profile and outcome is not well investigated.

Material And Methods: The German nationwide inpatient sample of the years 2005-2018 was analyzed. Hospitalized PE patients were stratified for diabetes, and the impact of diabetes on in-hospital events was investigated.

Results: Overall, 1,174,196 PE patients (53.8% aged ≥70 years, 53.5% women) and, among these, 219,550 (18.7%) diabetes patients were included. In-hospital mortality rate amounted to 15.8%, and was higher in diabetes patients than in non-diabetes patients (19.8% vs 14.8%, P < 0.001). PE patients with diabetes had a higher prevalence of cardiovascular risk factors, comorbidities, right ventricular dysfunction (31.8% vs 27.7%, P < 0.001), prolonged in-hospital stay (11.0 vs 9.0 days, P < 0.001) and higher rates of adverse in-hospital events. Remarkably, diabetes was independently associated with increased in-hospital mortality (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.20-1.23, P < 0.001) when adjusted for age, sex and comorbidities. Within the observation period of 2005-2018, a relevant decrease of in-hospital mortality in PE patients with diabetes was observed (25.5% to 16.8%). Systemic thrombolysis was more often administered to diabetes patients (OR 1.18, 95% CI 1.01-3.49, P < 0.001), and diabetes was associated with intracerebral (OR 1.19, 95% CI 1.12-1.26, P < 0.001), as well as gastrointestinal bleeding (OR 1.11, 95% CI 1.07-1.15, P < 0.001). Type 1 diabetes mellitus was shown to be a strong risk factor in PE patients for shock, right ventricular dysfunction, cardiopulmonary resuscitation and in-hospital death (OR 1.75, 95% CI 1.61-1.90, P < 0.001).

Conclusions: Despite the progress in diabetes treatments, diabetes is still associated with an unfavorable clinical patient profile and higher risk for adverse events, including substantially increased in-hospital mortality in acute PE.
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http://dx.doi.org/10.1111/jdi.13710DOI Listing
November 2021

Diabetes Mellitus and Its Impact on Patient-Profile and In-Hospital Outcomes in Peripheral Artery Disease.

J Clin Med 2021 Oct 28;10(21). Epub 2021 Oct 28.

Department of Cardiology, Cardiology I, University Medical Center Mainz (Johannes Gutenberg-University Mainz), 55131 Mainz, Germany.

Background: In patients with peripheral artery disease (PAD), the impact of diabetes mellitus (DM) on patient-profile and adverse in-hospital events is not well investigated.

Methods: The German nationwide inpatient sample 2005-2019 was used for this analysis. Hospitalized PAD patients were stratified for DM and the influence of DM on patient-profile and adverse in-hospital events was investigated.

Results: Our study comprised 2,654,871 hospitalizations (54.3% aged ≥70 years, 36.7% females) of patients with PAD in Germany 2005-2019. Among these, 864,691 (32.6%) patients had DM and 76,716 (2.9%) died during hospitalization. Diabetic PAD patients revealed an aggravated cardiovascular profile (Charlson Comorbidity Index: 6.0 (5.0-8.0) vs. 4.0 (3.0-5.0), < 0.001). PAD patients with DM showed a higher rate of in-hospital mortality (3.5% vs. 2.6%, < 0.001), as well as major adverse cardiovascular and cerebrovascular events (MACCE, 4.7% vs. 3.3%, < 0.001) and had more often operated with amputation surgery (16.4% vs. 9.1%, < 0.001). DM was an independent predictor of in-hospital mortality (OR 1.077 (95%CI 1.060-1.093), < 0.001) and MACCE (OR 1.118 (95%CI 1.103-1.133), < 0.001). In addition, amputations were also associated with DM (OR 1.804 (95%CI 1.790-1.818)), < 0.001).

Conclusions: DM is associated with an unfavorable clinical patient-profile and higher risk for adverse events in PAD patients, including substantially increased in-hospital mortality as well as MACCE rate, and were more often associated with amputation surgeries.
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http://dx.doi.org/10.3390/jcm10215033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8585025PMC
October 2021

Clinical use and outcome of extracorporeal membrane oxygenation in patients with pulmonary embolism.

Resuscitation 2021 Oct 12. Epub 2021 Oct 12.

Department of Cardiology, University Medical Center Mainz, Germany; Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Germany; Medical Clinic VII, University Hospital Heidelberg, Germany.

Aim Of The Study: Extracorporeal membrane oxygenation (ECMO) is considered a life-saving treatment option for patients in cardiogenic shock or cardiac arrest undergoing cardiopulmonary resuscitation (CPR) due to acute pulmonary embolism (PE). We sought to analyze use and outcome of ECMO with or without adjunctive treatment strategies in patients with acute PE.

Methods: We retrospectively analyzed data on patient characteristics, treatments, and in-hospital outcomes for all PE patients (ICD-code I26) undergoing ECMO in Germany between 2005 and 2018.

Results: At total of 1,172,354 patients were hospitalized with PE; of those, 2,197 (0.2%) were treated with ECMO support. Cardiac arrest requiring cardiopulmonary resuscitation was present in 77,196 (6.5%) patients. While more than one fourth of those patients were treated with systemic thrombolysis alone (n = 20,839 patients; 27.0%), a minority of patients received thrombolysis and VA-ECMO (n = 165; 0.2%), embolectomy and VA-ECMO (n = 385; 0.5%) or VA-ECMOalone (n = 588; 0.8%). A multivariable logistic regression analysis indicated the lowest risk for in-hospital death in patients who received embolectomy in combination with VA-ECMO (OR, 0.50 [95% CI, 0.41-0.61], p < 0.001), thrombolysis and VA-ECMO (0.60 [0.43-0.85], p = 0.003) or VA-ECMO alone (0.68 [0.57-0.82], p < 0.001) compared to thrombolysis alone (1.04 [0.99-1.01], p = 0.116).

Conclusion: Our findings suggest that the use of VA-ECMO alone or as part of a multi-pronged reperfusion approach including embolectomy or thrombolysis might offer survival advantages compared to thrombolysis alone in patients with PE deteriorating to cardiac arrest.
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http://dx.doi.org/10.1016/j.resuscitation.2021.10.007DOI Listing
October 2021

Early symptomatic benefit indicates long-term prognosis after transcatheter mitral valve edge-to-edge repair in functional and degenerative etiology.

Int J Cardiol 2021 Dec 23;344:141-146. Epub 2021 Sep 23.

Department of Cardiology, Cardiology I, University Medical Center Mainz (Johannes Gutenberg-University Mainz), Mainz, Germany. Electronic address:

Background: Mitral regurgitation (MR) is common in patients with heart failure and constitutes an independent risk factor for adverse prognosis besides NYHA-class. The predictive value of dyspnea reduction after transcatheter mitral valve repair (TMVr) on outcome has not been investigated up to now.

Methods And Results: We enrolled 627 consecutive patients (47.0% female, 57.4% functional MR; median follow-up 486 days[IQR 157/961]; survival status available in 96.8%; symptoms assessed in n = 556 at baseline / n = 406 at 1 month) treated with isolated percutaneous mitral valve edge-to-edge repair in our center from 06/2010-03/2018 (exclusion of combined forms of TMVr) in a monocentric retrospective analysis. Survival was 97.6% at discharge, 73.9% after 1, 54.5% after 3, 37.6% after 5 and 21.7% after 7-years. Before TMVr, NYHA-classes III/IV were found in 89.0%. Of these, 74.7% reported symptomatic relief (reduction in NYHA-class) one month after procedure (NYHA class recorded in 406 patients at 30 days). NYHA-classes III/IV were documented in 37.2% (p < 0.001) at 30 days and in 36.6% (p < 0.001) at 1 year without significant changes between the follow-ups. Dyspnea reduction was accompanied by significantly improved long-term survival (1 year, 89.1 vs 71.2%, p = 0.001, 2 years: 75.5 vs 58.7%, p = 0.039) and was identified as an independent predictor for lower mortality (1-year HR for increased mortality by missing symptomatic improvement 2.94 [95%CI 1.53-5.65], p = 0.001; long-term HR 1.95 [95%CI 1.29-2.94], p = 0.001) independently in both etiologies of MR.

Conclusion: TMVr by edge-to-edge therapy enables early and sustainable symptomatic improvement in nearly 75% of the symptomatic patients. The simple assessment of postinterventional changes in NYHA-class might serve as an independent predictor for mid- and long-term prognosis in both FMR and DMR.
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http://dx.doi.org/10.1016/j.ijcard.2021.09.038DOI Listing
December 2021

Galectin-3 for prediction of cardiac function compared to NT-proBNP in individuals with prediabetes and type 2 diabetes mellitus.

Sci Rep 2021 09 24;11(1):19012. Epub 2021 Sep 24.

German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany.

Use of galectin-3 for assessing cardiac function in prediabetes and type 2 diabetes mellitus (T2DM) needs to be established. Within the Gutenberg Health Study cohort (N = 15,010, 35-74 years) patient characteristics were investigated regarding galectin-3 levels. Prognostic value of galectin-3 compared to NT-proBNP concerning cardiac function and mortality was assessed in individuals with euglycaemia, prediabetes and T2DM in 5 years follow-up. Higher galectin-3 levels related to older age, female sex and higher prevalence for prediabetes, T2DM, cardiovascular risk factors and comorbidities. Galectin-3 cross-sectionally was related to impaired systolic (β - 0.36, 95% CI - 0.63/- 0.09; P = 0.008) and diastolic function (β 0.014, 95% CI 0.001/0.03; P = 0.031) in T2DM and reduced systolic function in prediabetes (β - 0.34, 95% CI - 0.53/- 0.15; P = 0.00045). Galectin-3 prospectively related to systolic (β - 0.656, 95% CI - 1.07/- 0.24; P = 0.0021) and diastolic dysfunction (β 0.0179, 95% CI 0.0001/0.036; P = 0.049), cardiovascular (hazard ratio per standard deviation of galectin-3 (HR) 1.60, 95% CI 1.39-1.85; P < 0.0001) and all-cause mortality (HR 1.36, 95% CI 1.25-1.47; P < 0.0001) in T2DM. No relationship between galectin-3 and cardiac function was found in euglycaemia, whereas NT-proBNP consistently related to reduced cardiac function. Prospective value of NT-proBNP on cardiovascular and all-cause mortality was higher. NT-proBNP was superior to galectin-3 to assess reduced systolic and diastolic function.
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http://dx.doi.org/10.1038/s41598-021-98227-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463561PMC
September 2021

Impact of Systemic Atherosclerosis on Clinical Characteristics and Short-term Outcomes in Patients with Deep Venous Thrombosis or Thrombophlebitis.

Am J Med Sci 2021 Sep 19. Epub 2021 Sep 19.

Department of Cardiology, Cardiology I, University Medical Center Mainz (Johannes Gutenberg-University Mainz), Mainz, Germany.

Background: Venous thromboembolism (VTE) and atherosclerosis are accompanied by substantial cardiovascular mortality; links between both disease entities were reported. We aimed to investigate the impact of systemic atherosclerosis on adverse outcomes in patients with deep venous thrombosis or thrombophlebitis (DVT) and to identify differences in DVT patients with and without systemic atherosclerosis.

Methods: The German nationwide inpatient sample was used for this analysis. Patients admitted for DVT were included in this study and stratified by systemic atherosclerosis (composite of coronary artery disease, myocardial infarction, ischemic stroke, and/or atherosclerotic arterial diseases). We compared DVT patients with (DVT+Athero) and without (DVT-Athero) systemic atherosclerosis and analysed the impact of systemic atherosclerosis on adverse outcomes.

Results: Overall, 489,679 patients with DVT (55.7% females) were included in this analysis. Among these, 53,309 (10.9%) were coded with concomitant systemic atherosclerosis with age-dependent incline. Concomitant PE (4.1% vs.3.8%, P=0.001) was more frequently in DVT-Athero and risk for PE in DVT patients was independently associated with absence of systemic atherosclerosis (OR 0.87 [95%CI 0.83-0.91], P<0.001). In-hospital mortality (3.4% vs.1.4%, P<0.001) and adverse in-hospital events (2.2% vs.0.8%,P<0.001) were more prevalent in DVT+Athero compared to DVT-Athero; both, in-hospital mortality (OR 1.52 [95%CI 1.41-1.63], P<0.001) and adverse in-hospital events (OR 1.49 [95%CI 1.40-1.58], P<0.001) were affected independently of sex, age and comorbidities by systemic atherosclerosis.

Conclusions: Systemic atherosclerosis in DVT patients was accompanied by poorer outcomes. Systemic atherosclerosis was associated with higher bleeding rate and with isolated DVT (without concomitant PE).
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http://dx.doi.org/10.1016/j.amjms.2021.09.002DOI Listing
September 2021

Disturbed Glucose Metabolism and Left Ventricular Geometry in the General Population.

J Clin Med 2021 Aug 27;10(17). Epub 2021 Aug 27.

German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, 55131 Mainz, Germany.

Background: This study sought to investigate the prevalence and clinical outcome of left ventricular (LV) geometry in prediabetes and type 2 diabetes mellitus (T2DM) and the impact of glucose metabolism on the incidence of left ventricular hypertrophy (LVH).

Methods: 15,010 subjects (35-74 years) of the population-based Gutenberg Health Study were categorized into euglycemia, prediabetes, and T2DM according to clinical and metabolic (HbA1c) information. Clinical outcome was assessed via structured follow-up.

Results: The study comprised 12,121 individuals with euglycemia (81.6%), 1415 with prediabetes (9.5%), and 1316 with T2DM (8.9%). Prevalence of LVH increased from euglycemia (10.2%) over prediabetes (17.8%) to T2DM (23.8%). Prediabetes and T2DM were associated with increased LV mass index (prediabetes: β1.3 (95% CI 0.78-1.81), < 0.0001; T2DM: β2.37 (95% CI 1.81; 2.92), < 0.0001) independent of age, sex, and cardiovascular risk factors (CVRF). The frequency of LVH was related to the presence of T2DM (prevalence ratio (PR)T2DM 1.2 (95% CI 1.06-1.35), = 0.0038). T2DM was related to mortality independent of age, sex, and CVRF regardless of LVH (hazard ratio (HR)T2DM-LVH 2.67 (95% CI 1.94-3.66), < 0.0001; HRT2DM-noLVH 1.59 (95% CI 1.29-1.96), < 0.0001), prediabetes was only associated with outcome in individuals with LVH independent of age and sex (HRprediabetes-LVH 1.51 (95% CI 1.01-2.25), = 0.045). Neither T2DM nor prediabetes were predictors of incident LVH after adjustment for clinical covariates.

Conclusions: Prediabetes and T2DM promote alterations of cardiac geometry. T2DM and particularly the coprevalence of T2DM with LVH substantially reduce life expectancy. These findings highlight the need for new therapeutic and screening approaches to prevent and detect cardiometabolic diseases at an early stage.
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http://dx.doi.org/10.3390/jcm10173851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432105PMC
August 2021

Psoriasis and its impact on the clinical outcome of patients with pulmonary embolism.

Int J Cardiol 2021 Nov 1;343:114-121. Epub 2021 Sep 1.

Department of Cardiology, Cardiology I, University Medical Center Mainz (Johannes Gutenberg-University Mainz), Mainz, Germany.; Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz (Johannes Gutenberg-University Mainz), Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Rhine Main, Mainz, Germany.

Background: An increased risk for venous thromboembolism (VTE), comprising pulmonary embolism (PE) and deep venous thrombosis, has been reported in psoriasis patients. The impact of psoriasis on prognosis of VTE patients is widely unknown.

Methods: Hospitalized PE patients were stratified for psoriasis and the impact of psoriasis on outcome was investigated in the German nationwide inpatient sample of the years 2005-2017.

Results: Overall, 1,076,384 hospitalizations of PE patients (53.7% females, median age 72.0 [60.0-80.0] years) were recorded in Germany 2005-2017. Among these, 3145 patients had psoriasis (0.3%). Psoriatic PE patients were younger (68.0 [57.0-76.0] vs. 72.0 [60.0-80.0] years,P < 0.001) and more often male (64.1% vs. 46.3%,P < 0.001). The prevalence of VTE risk factors, traditional cardiovascular risk factors and cardiovascular comorbidities was higher in psoriatic than in non-psoriatic individuals. Psoriatic PE patients showed a lower in-hospital case-fatality rate (11.1% vs. 16.0%,P < 0.001), confirmed by logistic regressions showing an independent association of psoriasis with reduced case-fatality rate (OR 0.73 [95%CI 0.65-0.82],P < 0.001), despite higher prevalence of pneumonia (24.8% vs. 23.2%,P = 0.029). Psoriasis was an independent predictor for gastro-intestinal bleeding (OR 1.35 [95%CI 1.04-1.75],P = 0.023) and transfusion of blood constituents (OR 1.23 [95%CI 1.11-1.36],P < 0.001).

Conclusions: PE patients with psoriasis were hospitalized in median four years earlier than those without. Although psoriasis was associated with an unfavorable cardiovascular-risk and VTE-risk profile in PE patients, our data demonstrate a lower in-hospital mortality in psoriatic PE, which might be mainly driven by younger age. Our findings may improve the clinical management of these patients and contribute evidence for relevant systemic manifestation of psoriasis.

Translational Perspective: An increased risk for venous thromboembolism (VTE), comprising pulmonary embolism (PE) and deep venous thrombosis, has been reported in psoriasis patients, but the impact of psoriasis on prognosis of VTE patients is widely unknown. PE patients with psoriasis were younger and psoriasis was associated with an unfavorable cardiovascular-risk and VTE-risk profile. In-hospital mortality was lower in psoriatic PE patients, which might be mainly driven by younger age. Our findings improve the clinical management of PE patients and contribute evidence for relevant systemic manifestation of psoriasis.

One Sentence Summary: Psoriasis with chronic inflammation promotes PE development, is associated with an unfavorable cardiovascular and VTE-risk profile, but lower in-hospital mortality.
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http://dx.doi.org/10.1016/j.ijcard.2021.08.042DOI Listing
November 2021

Generalized Ordinal Patterns and the KS-Entropy.

Entropy (Basel) 2021 Aug 23;23(8). Epub 2021 Aug 23.

Institute of Mathematics, University of Lübeck, D-23562 Lübeck, Germany.

Ordinal patterns classifying real vectors according to the order relations between their components are an interesting basic concept for determining the complexity of a measure-preserving dynamical system. In particular, as shown by C. Bandt, G. Keller and B. Pompe, the permutation entropy based on the probability distributions of such patterns is equal to Kolmogorov-Sinai entropy in simple one-dimensional systems. The general reason for this is that, roughly speaking, the system of ordinal patterns obtained for a real-valued "measuring arrangement" has high potential for separating orbits. Starting from a slightly different approach of A. Antoniouk, K. Keller and S. Maksymenko, we discuss the generalizations of ordinal patterns providing enough separation to determine the Kolmogorov-Sinai entropy. For defining these generalized ordinal patterns, the idea is to substitute the basic binary relation ≤ on the real numbers by another binary relation. Generalizing the former results of I. Stolz and K. Keller, we establish conditions that the binary relation and the dynamical system have to fulfill so that the obtained generalized ordinal patterns can be used for estimating the Kolmogorov-Sinai entropy.
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http://dx.doi.org/10.3390/e23081097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392665PMC
August 2021

[Trends in mortality related to pulmonary embolism in the DACH countries].

Med Klin Intensivmed Notfmed 2021 Aug 24. Epub 2021 Aug 24.

Centrum für Thrombose und Hämostase (CTH), Universitätsmedizin Mainz, Langenbeckstraße 1, 55131, Mainz, Deutschland.

Background: Pulmonary embolism (PE)-related mortality is decreasing worldwide.

Aim: Little is known about the burden imposed by pulmonary embolism for Germany, Austria and Switzerland (DACH countries).

Materials And Methods: We aimed to assess pulmonary embolism-related mortality and time trends for the DACH countries based on data from the WHO Mortality Database. Deaths were considered pulmonary embolism-related if the International Classification of Disease-10 code for acute pulmonary embolism or any code for deep or superficial vein thrombosis was listed as the primary cause of death.

Results: Between 2000 and 2015, age-standardized annual pulmonary embolism-related mortality rates decreased linearly from 15.6 to 7.8 deaths per 1000 population. In the 5‑year period between 2012 and 2016, an average of 9127 pulmonary embolism-related deaths occurred annually in the DACH countries with a population of 98,273,329. Interestingly, pulmonary embolism-related mortality rates were considerably higher among women aged 15-55 years compared to age-matched men.

Conclusion: The observed decreasing trends in pulmonary embolism-related mortality might reflect improved management of the disease including new treatment options as well as advances in imaging technologies. However, pulmonary embolism remains a substantial contributor to total mortality, especially among women aged 15-55 years. For this reason, campaigns to increase physician and public awareness are urgently required to further improve the management and treatment of this preventable thrombotic disorder, which still remains the leading preventable cause of death.
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http://dx.doi.org/10.1007/s00063-021-00854-9DOI Listing
August 2021

Temporal trends and predictors of inhospital death in patients hospitalised for heart failure in Germany.

Eur J Prev Cardiol 2021 Aug;28(9):990-997

Department of Cardiology, University Medical Center Mainz (Johannes Gutenberg-University Mainz), Germany.

Aims: We investigated trends in incidence, case fatality rate, patient characteristics and adverse inhospital events of patients hospitalised for heart failure in Germany.

Methods And Results: The German nationwide inpatient sample (2005-2016) was used for this analysis. Patients hospitalised due to heart failure were selected for analysis. Temporal trends in the incidence of hospitalisations, case fatality rate and treatments were analysed and predictors of inhospital death were identified. The analysis comprised a total number of 4,539,140 hospitalisations (52.0% women, 81.0% aged ≥70 years) due to heart failure. Although hospitalisations increased from 381 (2005) to 539 per 100,000 population (2016) (β estimate 0.06, 95% confidence interval (CI) 0.06 to 0.07, P < 0.001) in parallel with median age and prevalence of comorbidities, the inhospital case fatality rate decreased from 11.1% to 8.1% (β estimate -0.36, 95% CI -0.37 to -0.35, P < 0.001) and the rate of major adverse cardiovascular and cerebrovascular events (β estimate -0.24, 95% CI -0.25 to -0.23, P < 0.001) decreased from 12.7% to 10.3%. Age 70 years and older (odds ratio (OR) 2.60, 95% CI 2.57 to 2.63, P < 0.001) and cancer (OR 1.93, 95% CI 1.91 to 1.96, P < 0.001) were independent predictors of inhospital death.

Conclusion: Hospitalisations for heart failure increased in Germany from 2005 to 2016, whereas the major adverse cardiovascular and cerebrovascular event rate and inhospital case fatality rate decreased during this period despite higher patient age and increasing prevalence of comorbidities.
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http://dx.doi.org/10.1177/2047487320936020DOI Listing
August 2021

Cardiovascular profiling in the diabetic continuum: results from the population-based Gutenberg Health Study.

Clin Res Cardiol 2021 Jun 24. Epub 2021 Jun 24.

Department of Cardiology - Cardiology I, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.

Aims: To assess the prevalence of type 2 diabetes mellitus (T2DM) and prediabetes in the general population and to investigate the associated cardiovascular burden and clinical outcome.

Methods And Results: The study sample comprised 15,010 individuals aged 35-74 years of the population-based Gutenberg Health Study. Subjects were classified into euglycaemia, prediabetes and T2DM according to clinical and metabolic (HbA1c) information. The prevalence of prediabetes was 9.5% (n = 1415) and of T2DM 8.9% (n = 1316). Prediabetes and T2DM showed a significantly increased prevalence ratio (PR) for age, obesity, active smoking, dyslipidemia, and arterial hypertension compared to euglycaemia (for all, P < 0.0001). In a robust Poisson regression analysis, prediabetes was established as an independent predictor of clinically-prevalent cardiovascular disease (PR 1.20, 95% CI 1.07-1.35, P = 0.002) and represented as a risk factor for asymptomatic cardiovascular organ damage independent of traditional risk factors (PR 1.04, 95% CI 1.01-1.08, P = 0.025). Prediabetes was associated with a 1.5-fold increased 10-year risk for cardiovascular disease compared to euglycaemia. In Cox regression analysis, prediabetes (HR 2.10, 95% CI 1.76-2.51, P < 0.0001) and T2DM (HR 4.28, 95% CI 3.73-4.92, P < 0.0001) indicated for an increased risk of death. After adjustment for age, sex and traditional cardiovascular risk factors, only T2DM (HR 1.89, 95% CI 1.63-2.20, P < 0.0001) remained independently associated with increased all-cause mortality.

Conclusion: Besides T2DM, also prediabetes inherits a significant cardiovascular burden, which translates into poor clinical outcome and indicates the need for new concepts regarding the prevention of cardiometabolic disorders.
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http://dx.doi.org/10.1007/s00392-021-01879-yDOI Listing
June 2021

Total numbers and in-hospital mortality of patients with myocardial infarction in Germany during the FIFA soccer world cup 2014.

Sci Rep 2021 06 17;11(1):11330. Epub 2021 Jun 17.

Medical Clinic VII, Department of Sports Medicine, University Hospital Heidelberg, Heidelberg, Germany.

Environmental stress like important soccer events can induce excitation, stress and anger. We aimed to investigate (i) whether the FIFA soccer world cup (WC) 2014 and (ii) whether the soccer games of the German national team had an impact on total numbers and in-hospital mortality of patients with myocardial infarction (MI) in Germany. We analyzed data of MI inpatients of the German nationwide inpatient sample (2013-2015). Patients admitted due to MI during FIFA WC 2014 (12th June-13th July2014) were compared to those during the same period 2013 and 2015 (12th June-13th July). Total number of MI patients was higher during WC 2014 than in the comparison-period 2013 (18,479 vs.18,089, P < 0.001) and 2015 (18,479 vs.17,794, P < 0.001). WC was independently associated with higher MI numbers (2014 vs. 2013: OR 1.04 [95% CI 1.01-1.07]; 2014 vs. 2015: OR 1.07 [95% CI 1.04-1.10], P < 0.001). Patient characteristics and in-hospital mortality rate (8.3% vs. 8.3% vs. 8.4%) were similar during periods. In-hospital mortality rate was not affected by games of the German national team (8.9% vs. 8.1%, P = 0.110). However, we observed an increase regarding in-hospital mortality from 7.9 to 9.3% before to 12.0% at final-match-day. Number of hospital admissions due to MI in Germany was 3.7% higher during WC 2014 than during the same 31-day period 2015. While in-hospital mortality was not affected by the WC, the in-hospital mortality was highest at WC final.
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http://dx.doi.org/10.1038/s41598-021-90582-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211804PMC
June 2021

Prognostic value of right atrial dilation in patients with pulmonary embolism.

ERJ Open Res 2021 Apr 24;7(2). Epub 2021 May 24.

Dept of Internal Medicine and Cardiology, Charité - University Medicine Berlin, Berlin, Germany.

Aims: Right atrial (RA) dilation and stretch provide prognostic information in patients with cardiovascular diseases. We investigated the prevalence, confounding factors and prognostic relevance of RA dilation in patients with pulmonary embolism (PE).

Methods: Overall, 609 PE patients were consecutively included in a prospective single-centre registry between September 2008 and August 2017. Volumetric measurements of heart chambers were performed on routine non-electrocardiographic-gated computed tomography and plasma concentrations of mid-regional pro-atrial natriuretic peptide (MR-proANP) measured on admission. An in-hospital adverse outcome was defined as PE-related death, cardiopulmonary resuscitation, mechanical ventilation or catecholamine administration.

Results: Patients with an adverse outcome (11.2%) had larger RA volumes (median 120 (interquartile range 84-152) 102 (78-134) mL; p=0.013), RA/left atrial (LA) volume ratios (1.7 (1.2-2.4) 1.3 (1.1-1.7); p<0.001) and MR-proANP levels (282 (157-481) 129 (64-238) pmol·L; p<0.001) compared to patients with a favourable outcome. Overall, 499 patients (81.9%) had a RA/LA volume ratio ≥1.0 and a calculated cut-off value of 1.8 (area under the curve 0.64, 95% CI 0.56-0.71) predicted an adverse outcome, both in unselected (OR 3.1, 95% CI 1.9-5.2) and normotensive patients (OR 2.7, 95% CI 1.3-5.6). MR-proANP ≥120 pmol·L was identified as an independent predictor of an adverse outcome, both in unselected (OR 4.6, 95% CI 2.3-9.3) and normotensive patients (OR 5.1, 95% CI 1.5-17.6).

Conclusions: RA dilation is a frequent finding in patients with PE. However, the prognostic performance of RA dilation appears inferior compared to established risk stratification markers. MR-proANP predicted an in-hospital adverse outcome, both in unselected and normotensive PE patients, integrating different prognostic relevant information from comorbidities.
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http://dx.doi.org/10.1183/23120541.00414-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141828PMC
April 2021

Time trends of pulmonary endarterectomy in patients with chronic thromboembolic pulmonary hypertension.

Pulm Circ 2021 Apr-Jun;11(2):20458940211008069. Epub 2021 Apr 28.

Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Mainz, Germany.

Chronic thromboembolic pulmonary hypertension is considered as a rare but severe complication after acute pulmonary embolism and is potentially curable by pulmonary endarterectomy. We aimed to evaluate, over an 11-year period, time trends of in-hospital outcomes of pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension patients and to investigate predictors of the in-hospital course. We analyzed data on the characteristics, comorbidities, treatments, and in-hospital outcomes for all chronic thromboembolic pulmonary hypertension patients treated with pulmonary endarterectomy in the German nationwide inpatient sample between 2006 and 2016. Overall, 1398 inpatients were included. Annual number of pulmonary endarterectomy increased from 67 in 2006 to 194 in 2016 ( < 0.001), in parallel with a significant decrease of in-hospital mortality (10.9% in 2008 to 1.5% in 2016;  < 0.001). Patients' characteristics shifted slightly toward older age and higher prevalence of chronic renal insufficiency and obesity over time, whereas duration of hospital stay decreased over time. Independent predictors of in-hospital mortality were age (OR 1.03 (95%CI: 1.01-1.05);  = 0.001), right heart failure (2.55 (1.37-4.76);  = 0.003), in-hospital complications such as ischemic stroke (6.87 (1.06-44.70);  = 0.044) and bleeding events like hemopneumothorax (24.93 (6.18-100.57);  < 0.001). Annual pulmonary endarterectomy volumes per center below 10 annual procedures were associated with higher rates of adverse in-hospital outcomes. Annual numbers of chronic thromboembolic pulmonary hypertension patients treated with pulmonary endarterectomy increased markedly in Germany between 2006 and 2016, in parallel with a decrease of in-hospital mortality. Our findings suggest that perioperative management of pulmonary endarterectomy, institutional experience, and patient selection is crucial and has improved over time.
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http://dx.doi.org/10.1177/20458940211008069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108078PMC
April 2021

Centre procedural volume and adverse in-hospital outcomes in patients undergoing percutaneous transvenous edge-to-edge mitral valve repair using MitraClip® in Germany.

Eur J Heart Fail 2021 08 3;23(8):1380-1389. Epub 2021 May 3.

Department of Cardiology, Cardiology I, University Medical Center Mainz, Mainz, Germany.

Aims: The number of transcatheter mitral valve repair (TMVr) procedures has increased substantially during the last years. A better understanding of the relationship between hospital volume of transcatheter transvenous mitral valve repairs using MitraClip® and patient outcomes may provide information for future policy decisions to improve patient management.

Methods And Results: We analysed patient characteristics and in-hospital outcomes for all TMVr procedures using MitraClip® performed in Germany from 2011 to 2017. Hospitals were stratified according to centre volumes and patients were compared for baseline characteristics and adverse in-hospital events. Overall, 24 709 inpatients were treated during the observational period. Patients treated in centres with a volume of ≤10 procedures annually developed more often pulmonary embolism (odds ratio 2.22, 95% confidence interval 1.19-4.13; P = 0.012) compared to those treated in centres with a volume of >10 procedures annually, whereas no association of centre volume (≤10 or >10) was found with in-hospital mortality (P = 0.728). Although patients treated in centres with an annual volume >25 TMVr procedures had higher numbers of comorbidities compared to those treated in centres with an annual volume of ≤25 TMVr procedures, in-hospital mortality did not differ (3.6% vs. 3.5%, P = 0.485). Similarly, when centre volumes were stratified for ≤50 vs. >50 procedural volumes, no association with in-hospital mortality was recorded (P = 0.792). A lower rate of mitral valve surgery after MitraClip® was observed over time, particularly in high-volume centres.

Conclusion: Annual numbers of MitraClip® implantations increased from 2011 to 2017 in Germany, whereas in-hospital mortality remained stable. Although patients treated in high-volume centres had a more unfavourable risk profile, in-hospital mortality was comparable to that of low-volume centres.
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http://dx.doi.org/10.1002/ejhf.2162DOI Listing
August 2021

In-hospital outcomes of catheter-directed thrombolysis in patients with pulmonary embolism.

Eur Heart J Acute Cardiovasc Care 2021 May;10(3):258-264

Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz (Johannes Gutenberg University Mainz), Langenbeckstrasse 1, 55131 Mainz, Germany.

Aims: Catheter-directed treatment of acute pulmonary embolism (PE) is technically advancing. Recent guidelines acknowledge this treatment option for patients with overt or imminent haemodynamic decompensation, particularly when systemic thrombolysis is contraindicated. We investigated patients with PE who underwent catheter-directed thrombolysis (CDT) in the German nationwide inpatient cohort.

Methods And Results: Data from hospitalizations with PE (International Classification of Disease code I26) between 2005 and 2016 were collected by the Federal Office of Statistics in Germany. Patients with PE who underwent CDT (OPS 8-838.60 or OPS code 8-83b.j) were compared with patients receiving systemic thrombolysis (OPS code 8-020.8), and those without thrombolytic or other reperfusion treatment. The analysis was not prespecified; therefore, our findings can only be considered to be hypothesis generating. We analysed data from 978 094 hospitalized patients with PE. Of these, 41 903 (4.3%) patients received thrombolytic treatment [systemic thrombolysis in 4.2%, CDT in 0.1% (1175 patients)]. Among patients with shock, CDT was associated with lower in-hospital mortality compared to systemic thrombolysis [odds ratios (OR) 0.30 (95% 0.14-0.67); P = 0.003]. Intracranial bleeding occurred in 14 (1.2%) patients who received CDT. Among haemodynamically stable patients with right ventricular dysfunction (intermediate-risk PE), CDT also was associated with a lower risk of in-hospital mortality compared to systemic thrombolysis {OR 0.55 [95% confidence interval (CI) 0.40-0.75]; P < 0.001} or no thrombolytic treatment [0.45 (95% CI 0.33-0.62); P < 0.001].

Conclusion: In the German nationwide inpatient cohort, based on administrative data, CDT was associated with lower in-hospital mortality rates compared to systemic thrombolysis, but the overall rate of intracranial bleeding in patients who received CDT was not negligible. Prospective controlled data are urgently needed to determine the true value of this treatment option in acute PE.
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http://dx.doi.org/10.1093/ehjacc/zuaa026DOI Listing
May 2021

High-sensitivity troponin I for risk stratification in normotensive pulmonary embolism.

ERJ Open Res 2020 Oct 21;6(4). Epub 2020 Dec 21.

German Center for Cardiovascular Research (DZHK), partner site Berlin, Germany.

While numerous studies have confirmed the prognostic role of high-sensitivity troponin T (hsTnT) in pulmonary embolism (PE), high-sensitivity troponin I (hsTnI) is inappropriately studied. This study aimed to investigate the prognostic relevance of hsTnI in normotensive PE, establish the optimal cut-off value for risk stratification and to compare the prognostic performances of hsTnI and hsTnT. Based on data from 459 consecutive PE patients enrolled in a single-centre registry, receiver operating characteristic analysis was used to identify an optimal hsTnI cut-off value for prediction of in-hospital adverse outcomes (PE-related death, cardiopulmonary resuscitation or vasopressor treatment) and all-cause mortality. Patients who suffered an in-hospital adverse outcome (4.8%) had higher hsTnI concentrations compared with those with a favourable clinical course (57 (interquartile range (IQR) 22-197) 15 (IQR 10-86) pg·mL, p=0.03). A hsTnI cut-off value of 16 ng·mL provided optimal prognostic performance and predicted in-hospital adverse outcomes (OR 6.5, 95% CI 1.9-22.4) and all-cause mortality (OR 3.7, 95% CI 1.0-13.3). Between female and male patients, no relevant differences in hsTnI concentrations (17 (IQR 10-97) 17 (IQR 10-92) pg·mL, p=0.79) or optimised cut-off values were observed. Risk stratification according to the 2019 European Society of Cardiology algorithm revealed no differences if calculated based on either hsTnI or hsTnT (p=0.68). Our findings confirm the prognostic role of hsTnI in normotensive PE. HsTnI concentrations >16 pg·mL predicted in-hospital adverse outcome and all-cause mortality; sex-specific cut-off values do not seem necessary. Importantly, our results suggest that hsTnI and hsTnT can be used interchangeably for risk stratification.
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http://dx.doi.org/10.1183/23120541.00625-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792860PMC
October 2020

Concomitant tricuspid regurgitation severity and its secondary reduction determine long-term prognosis after transcatheter mitral valve edge-to-edge repair.

Clin Res Cardiol 2021 May 12;110(5):676-688. Epub 2021 Jan 12.

Department of Cardiology, Cardiology I, University Medical Center Mainz (Johannes Gutenberg-University Mainz), Mainz, Germany.

Background: Concomitant tricuspid regurgitation (TR) is a common finding in mitral regurgitation (MR). Transcatheter repair (TMVR) is a favorable treatment option in patients at elevated surgical risk. To date, evidence on long-term prognosis and the prognostic impact of TR after TMVR is limited.

Methods: Long-term survival data of patients undergoing isolated edge-to-edge repair from June 2010 to March 2018 (combinations with other forms of TMVR or tricuspid valve therapy excluded) were analyzed in a retrospective monocentric study. TR severity was categorized and the impact of TR on survival was analysed.

Results: Overall, 606 patients [46.5% female, 56.4% functional MR (FMR)] were enrolled in this study. TR at baseline was categorized severe/medium/mild/no or trace in 23.2/34.3/36.3/6.3% of the cases. At 30-day follow-up, improvement of at least one TR-grade was documented in 34.9%. Severe TR at baseline was identified as predictor of 1-year survival [65.2% vs. 77.0%, p = 0.030; HR for death 1.68 (95% CI 1.12-2.54), p = 0.013] and in FMR-patients also regarding long-term prognosis [adjusted HR for long-term mortality 1.57 (95% CI 1.00-2.45), p = 0.049]. Missing post-interventional reduction of TR severity was predictive for poor prognosis, especially in the FMR-subgroup [1-year survival: 92.9% vs. 78.3%, p = 0.025; HR for death at 1-year follow-up 3.31 (95% CI 1.15-9.58), p = 0.027]. While BNP levels decreased in both subgroups, TR reduction was associated with improved symptomatic benefit (NYHA-class-reduction 78.6 vs. 65.9%, p = 0.021).

Conclusion: In this large study, both, severe TR at baseline as well as missing secondary reduction were predictive for impaired long-term prognosis, especially in patients with FMR etiology. TR reduction was associated with increased symptomatic benefit.
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http://dx.doi.org/10.1007/s00392-020-01798-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099767PMC
May 2021

Venous thromboembolism in patients hospitalized for knee joint replacement surgery.

Sci Rep 2020 12 31;10(1):22440. Epub 2020 Dec 31.

Department of Orthopaedics and Traumatology, University Medical Center Mainz (Johannes Gutenberg-University Mainz), Mainz, Germany.

Patients undergoing knee joint replacement (KJR) are at high risk of postoperative venous thromboembolism (VTE), but data on the time trends of VTE rate in this population are sparse. In this analysis of the German nationwide inpatient sample, we included all hospitalizations for elective primary KJR in Germany 2005-2016. Overall, 1,804,496 hospitalized patients with elective primary KJR (65.1% women, 70.0 years [IQR 63.0-76.0]) were included in the analysis. During hospitalization, VTE was documented in 23,297 (1.3%) patients. Total numbers of primary KJR increased from 129,832 in 2005 to 167,881 in 2016 (β-(slope)-estimate 1,978 [95% CI 1,951 to 2,004], P < 0.001). In-hospital VTE decreased from 2,429 (1.9% of all hospitalizations for KJR) to 1,548 (0.9%) cases (β-estimate - 0.77 [95% CI - 0.81 to - 0.72], P < 0.001), and in-hospital death rate from 0.14% (184 deaths) to 0.09% (146 deaths) (β-estimate - 0.44 deaths per year [95% CI - 0.59 to - 0.30], P < 0.001). Infections during hospitalization were associated with a higher VTE risk. VTE events were independently associated with in-hospital death (OR 20.86 [95% CI 18.78-23.15], P < 0.001). Annual number of KJR performed in Germany increased by almost 30% between 2005 and 2016. In parallel, in-hospital VTE rates decreased from 1.9 to 0.9%. Perioperative infections were associated with higher risk for VTE. Patients who developed VTE had a 21-fold increased risk of in-hospital death.
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http://dx.doi.org/10.1038/s41598-020-79490-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775461PMC
December 2020

Predictive value of the Kuijer score for bleeding and other adverse in-hospital events in patients with venous thromboembolism.

Int J Cardiol 2021 04 8;329:179-184. Epub 2020 Dec 8.

Department of Cardiology, Cardiology I, University Medical Center Mainz (Johannes Gutenberg-University Mainz), Mainz, Germany.

Background: Venous thromboembolism (VTE) constitute a major global burden of disease. Current international guidelines recommend treatment with anticoagulant therapy after VTE for a duration of at least 3 months. Since anticoagulation also imposes an increased risk for bleeding events, the individual risk has to be evaluated to determine adequate treatment plans.

Methods: The nationwide German inpatient sample of the years 2005-2017 was used for this analysis. Hospitalized VTE patients were stratified according to Kuijer risk class and the performance of the Kuijer score was evaluated to predict adverse in-hospital events.

Results: Overall, 1,204,895 VTE patients were treated between 2005 and 2017 in Germany and were included in the present study (839,143 patients had deep venous thrombosis and/or thrombophlebitis and 669,881 patients pulmonary embolism). According to Kuijer risk class stratification, in total, 176,723 (14.7%) of the hospitalized VTE patients were classified as low risk, 914,964 (75.9%) as intermediate risk and 113,208 (9.4%) as high risk. A higher Kuijer risk class was predictive for in-hospital death (odds ratio [OR] 1.99 [95% confidence interval (CI) 1.96-2.02], P < 0.001), major adverse cardiovascular and cerebrovascular events (MACCE, OR 1.90 [95%CI 1.87-1.93], P < 0.001), intracerebral bleeding (OR 1.28 [95%CI 1.14-1.44], P < 0.001), gastrointestinal bleeding (OR 1.56 [95%CI 1.48-1.64], P < 0.001) as well as necessity of transfusion of blood constituents (OR 2.94 [95%CI 2.88-3.00], P < 0.001) independently of important comorbidities.

Conclusions: The Kuijer score is an important risk stratification tool to predict individual risk regarding in-hospital outcomes comprising major bleeding events such as intracerebral bleeding and necessity of transfusion of blood constituents, but also in-hospital mortality and MACCE in VTE patients.
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http://dx.doi.org/10.1016/j.ijcard.2020.11.075DOI Listing
April 2021

Ordinal Pattern Based Entropies and the Kolmogorov-Sinai Entropy: An Update.

Entropy (Basel) 2020 Jan 2;22(1). Epub 2020 Jan 2.

Institute of Mathematics, University of Lübeck, D-23562 Lübeck, Germany.

Different authors have shown strong relationships between ordinal pattern based entropies and the Kolmogorov-Sinai entropy, including equality of the latter one and the permutation entropy, the whole picture is however far from being complete. This paper is updating the picture by summarizing some results and discussing some mainly combinatorial aspects behind the dependence of Kolmogorov-Sinai entropy from ordinal pattern distributions on a theoretical level. The paper is more than a review paper. A new statement concerning the conditional permutation entropy will be given as well as a new proof for the fact that the permutation entropy is an upper bound for the Kolmogorov-Sinai entropy. As a main result, general conditions for the permutation entropy being a lower bound for the Kolmogorov-Sinai entropy will be stated. Additionally, a previously introduced method to analyze the relationship between permutation and Kolmogorov-Sinai entropies as well as its limitations will be investigated.
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http://dx.doi.org/10.3390/e22010063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516495PMC
January 2020

Impact of diabetes mellitus on mortality rates and outcomes in myocardial infarction.

Diabetes Metab 2021 07 28;47(4):101211. Epub 2020 Nov 28.

Department of Cardiology, Cardiology I, University Medical Center Mainz (Johannes Gutenberg-University Mainz), Mainz, Germany; Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz (Johannes Gutenberg-University Mainz), Mainz, Germany; Medical Clinic VII, Department of Sports Medicine, University Hospital Heidelberg, Heidelberg, Germany. Electronic address:

Background: Diabetes mellitus (DM) represents a major cardiovascular risk factor for increased risk of coronary artery disease and myocardial infarction (MI). DM is also associated with a poorer clinical outcome in MI.

Materials And Methods: The nationwide German inpatient population treated between 2005 and 2016 was used for statistical analyses. Hospitalized MI patients were stratified by the presence of DM and investigated for the impact of DM on in-hospital events.

Results: In total, 3,307,703 hospitalizations for acute MI (37.6% female patients, 56.8% aged ≥ 70 years) treated in Germany during 2005-2016 were included in this analysis. Of these patients, 410,737 (12.4%) died while in hospital. Overall, 1,007,326 (30.5%) MI cases were coded for DM. While the rate of MI patients with DM increased slightly over time, from 29.8% in 2005 to 30.7% in 2016 (β = 7.04, 95% CI: 4.13-9.94; P <  0.001), their in-hospital mortality decreased from 15.2% to 11.5% (β = -0.36, 95% CI: -0.38 to -0.34; P <  0.001). Rates of in-hospital death (13.2% vs 12.1%; P <  0.001) and recurrent MI (0.8% vs 0.6%; P <  0.001) were higher in MI patients with vs without DM. Also, in MI patients with DM, significantly lower use of coronary artery angiography (51.5% vs 56.8%; P <  0.001) and interventional revascularization (37.6% vs 43.9%; P <  0.001) was noted.

Conclusion: Although in-hospital mortality of patients with MI decreased in both diabetes and non-diabetes patients, in-hospital deaths were still higher in diabetes patients, thereby revealing the impact of this metabolic disorder on cardiovascular outcomes.
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http://dx.doi.org/10.1016/j.diabet.2020.11.003DOI Listing
July 2021

Impact of atrial fibrillation/flutter on the in-hospital mortality of surgical patients - Results from the German nationwide cohort.

Thromb Res 2020 12 15;196:526-535. Epub 2020 Oct 15.

Department for Orthopedics, Trauma Surgery and Hand Surgery, Klinikum Osnabrück, Osnabrück, Germany; Institute for Applied Training Science Leipzig, Leipzig, Germany.

Background: To investigate the impact of atrial fibrillation/flutter (AF) on adverse in-hospital outcomes in hospitalized surgical patients.

Methods: The nationwide German inpatient sample of the years 2005-2018 was used for this analysis. Surgical patients were stratified by AF and compared. Logistic regression models were used to investigate the impact of AF on in-hospital outcomes.

Results: In total, 96,589,627 hospitalizations with surgery were included in the present analysis in Germany (2005-2018). Among these, 6,680,261 were additionally coded with AF (6.9%). In-hospital death rate was substantially higher in surgical patients with AF (6.3%) than without (1.1%). Proportion of surgical patients with AF increased from 4.8% in 2005 to 8.9% in 2018, whereas in-hospital mortality decreased from 7.6% to 5.6%. For further analysis of the year 2014, 7,043,514 hospitalized surgical patients (54.5% females, 31.6% aged ≥0 years) were included in the analysis. Of these, 546,019 patients (7.8%) were diagnosed with AF. Overall, 1.4% of the surgical patients and 5.8% of the surgical patients with AF died in-hospital. Surgical patients with coded AF were in median 20 years older (57.0 [37.0-72.0] vs. 77.0 [72.0-83.0] years, P < 0.001), had more often comorbidities such as heart failure (31.3% vs. 3.8%, P < 0.001). All-cause death (RR 6.14 (95%CI 6.05-6.22), P < 0.001) occurred more often in patients with AF than without. AF was an important predictor for in-hospital death (OR 1.58 [95%CI 1.56-1.61], P < 0.001) independent of age, sex and comorbidities.

Conclusions: The proportion of AF increased from 2005 to 2018 in surgical patients. AF was an independent risk factor for in-hospital death in these patients.
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http://dx.doi.org/10.1016/j.thromres.2020.10.015DOI Listing
December 2020

Telemedicine-Based Specialized Care Improves the Outcome of Anticoagulated Individuals with Venous Thromboembolism-Results from the thrombEVAL Study.

J Clin Med 2020 Oct 13;9(10). Epub 2020 Oct 13.

Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.

Venous thromboembolism (VTE) is a life-threatening disease with risk of recurrence. Oral anticoagulation (OAC) with vitamin K antagonists (VKA) is effective to prevent thromboembolic recurrence. We aimed to investigate the quality of OAC of VTE patients in regular medical care (RMC) compared to a telemedicine-based coagulation service (CS). The thrombEVAL study (NCT01809015) is a prospective, multi-center study to investigate OAC treatment (recruitment: January 2011-March 2013). Patients were evaluated using clinical visits, computer-assisted personal interviews, self-reported data and laboratory measurements according to standard operating procedures. Overall, 360 patients with VTE from RMC and 254 from CS were included. Time in therapeutic range (TTR) was higher in CS compared to RMC (76.9% (interquartile range [IQR] 63.2-87.1%) vs. 69.5% (52.3-85.6%), < 0.001). Crude rate of thromboembolic events (rate ratio [RR] 11.33 (95% confidence interval [CI] 1.85-465.26), = 0.0015), clinically relevant bleeding (RR 6.80 (2.52-25.76), < 0.001), hospitalizations (RR 2.54 (1.94-3.39), < 0.001) and mortality under OAC (RR 5.89 (2.40-18.75), < 0.001) were consistently higher in RMC compared with CS. Patients in RMC had higher risk for primary outcome (clinically relevant bleedings, thromboembolic events and mortality, hazard ratio [HR] 5.39 (95%CI 2.81-10.33), < 0.0001), mortality (HR 5.54 (2.22-13.84), = 0.00025), thromboembolic events (HR 6.41 (1.51-27.24), = 0.012), clinically relevant bleeding (HR 5.31 (1.89-14.89), = 0.0015) and hospitalization (HR 1.84 (1.34-2.55), = 0.0002). Benefits of CS care were still observed after adjusting for comorbidities and TTR. In conclusion, anticoagulation quality and outcome of VTE patients undergoing VKA treatment was significantly better in CS than in RMC. Patients treated in CS had lower rates of adverse events, hospitalizations and lower mortality. CS was prognostically relevant, beyond providing advantages of improved international ratio (INR) monitoring.
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http://dx.doi.org/10.3390/jcm9103281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602093PMC
October 2020

Impact of pulmonary embolism on in-hospital mortality of patients with ischemic stroke.

J Neurol Sci 2020 Dec 9;419:117174. Epub 2020 Oct 9.

Department of Cardiology, Cardiology I, University Medical Center Mainz (Johannes Gutenberg-University Mainz), Mainz, Germany.

Background: Pulmonary embolism (PE) is a frequent complication in immobile stroke patients and an important cause of death in stroke patients. We aimed to investigate predictors of PE and the impact of PE on survival of ischemic stroke patients.

Methods: Patients were selected by screening the German nationwide inpatient sample (2005-2017) for ischemic stroke (ICD-code I63) and stratified for occurrence of PE (ICD-code I26). Impact of PE on mortality and predictors for PE in ischemic stroke patients were analysed.

Results: Overall, 2,914,546 patients were hospitalized due to ischemic stroke (50.5% females; 69.3% aged ≥70 years) in Germany 2005-2017. Among these, 0.4% had PE and 7.2% died during hospitalization. In-hospital mortality rate of ischemic stroke patients with PE was substantially higher compared to those patients without PE (28.4% vs. 7.1%, P < 0.001). PE was strongly associated with in-hospital death (OR 5.786, 95%CI 5.515-6.070, P < 0.001). Important predictors of PE were cancer (OR 3.165, 95%CI 2.969-3.374, P < 0.001), coagulation abnormalities (OR 2.672, 95CI 2.481-2.878, P < 0.001), heart failure (OR 1.553, 95%CI 1.472-1.639, P < 0.001) and obesity (OR 1.559, 95%CI 1.453-1.672, P < 0.001). Systemic thrombolysis was not beneficial regarding survival in unselected ischemic stroke patients. In contrast, systemic thrombolysis was beneficial in ischemic stroke patients without PE, who had to undergo cardio-pulmonary resuscitation (OR 0.866, 95%CI 0.782-0.960, P = 0.006).

Conclusions: Patients with ischemic stroke revealed still a high in-hospital mortality of 7.2% in Germany. While only a minority of 0.4% of the ischemic stroke patients suffered from occurrence of PE, PE was accompanied by a substantial increase regarding in-hospital mortality. Systemic thrombolysis was beneficial regarding short-term survival in ischemic stroke patients without PE, who had to undergo cardio-pulmonary resuscitation.
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http://dx.doi.org/10.1016/j.jns.2020.117174DOI Listing
December 2020

Psoriasis and Its Impact on In-Hospital Outcome in Patients Hospitalized with Acute Kidney Injury.

J Clin Med 2020 Sep 17;9(9). Epub 2020 Sep 17.

Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz (Johannes Gutenberg-University Mainz), 55131 Mainz, Germany.

Background: Psoriasis is a chronic inflammatory disease which affects the body far beyond the skin. Whereas there is solid evidence that chronic skin inflammation in psoriasis drives cardiovascular disease, the impact on renal impairment and acute kidney injury (AKI) is still unclear. We aimed to analyze the impact of psoriasis on the in-hospital outcome of patients hospitalized with AKI.

Methods: In this retrospective database study, we investigated data on characteristics, comorbidities, and in-hospital outcomes for all hospitalized patients with AKI stratified for concomitant psoriasis, which were collected by the Federal Office of Statistics in Germany between 2005 and 2016.

Results: Among the 3,162,449 patients treated for AKI in German hospitals between 2005 and 2016, 11,985 patients (0.4%) additionally suffered from psoriasis. While the annual number of AKI patients with psoriasis increased significantly from 485 cases (4.0%) in 2005 to 1902 (15.9%) in 2016 ( < 0.001), the in-hospital mortality decreased substantially (from 24.9% in 2005 to 17.4% in 2016; < 0.001). AKI patients with concomitant psoriasis were younger (70 (IQR; 60-78) vs. 76 (67-83) years; < 0.001) and were more often treated with dialysis (16.3% vs. 13.6%, < 0.001). Presence of psoriasis in AKI patients was associated with reduced prevalence of myocardial infarction (OR 0.62; < 0.001), stroke (OR 0.85; = 0.013), and in-hospital mortality (OR 0.75; < 0.001).

Conclusions: AKI patients with psoriasis were hospitalized in median 6 years earlier than those without. Despite younger age, we detected higher use of kidney replacement therapy in patients with psoriasis, indicating a more severe course of AKI. Our findings might improve management of these patients and contribute evidence for extracutaneous, systemic manifestations of psoriasis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563226PMC
September 2020
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