TY  - THES
A1  - Werle, Philipp
T1  - Rolle von Mannose-binding Lectin für das ventrikuläre Remodeling nach Myokardinfarkt
T1  - The role of mannose-binding lectin in ventricular remodelling after myocardial infarction
N2  - Das aktivierte Komplementsystem, als Teil der angeborenen Immunantwort nach Myokardinfarkt, beeinflusst entscheidend das kardiale Remodeling. Mäuse, die für den Komplementfaktor C3 defizient waren, wiesen acht Wochen nach Infarkt eine signifikant geringere linksventrikuläre Dilatation auf. Anhand von MBL-KO Mäusen sollte in dieser Arbeit die Frage geklärt werden, inwieweit die Aktivierung des Komplementsystems im kardialen Remodeling auf den durch MBL eingeleiteten Pfad zurückgeht. Während sich bezüglich der Infarktgrößen, der Neutrophilen und des Kollagengehalts kein signifikanter Unterschied zwischen den beiden Gruppen zeigte, so wiesen die MBL-KO Tiere im Vergleich zu den WT Tieren eine signifikant größere ventrikuläre Dilatation auf. Basierend auf diesen Erkenntnissen kommen wir zu dem Schluss, dass sich die bezüglich der Ventrikelgröße positiven Effekte einer C3 Hemmung nicht mit einer MBL Hemmung in Einklang bringen lassen. Die dauerhafte Aktivierung des Komplementsystems während des ventrikulären Remodelings, beruht angesichts der Aggravierung der linksventrikulären Dilatation nicht auf dem MBL-Weg.
N2  - The complement system, as an important part of the activated innate immune system after myocardial infarction, influences the remodelling process. Complement factor C3-KO mice showed 8 weeks after infarction significant less ventricular dilatation than WT-mice. Here, we examined whether activation of the complement system in cardiac remodelling could be ascribed to the MBL pathway. However, 8 weeks after infarction MBL-KO mice showed a significant increase in ventricular dilatation compared to the WT-mice of the control group. The positive effects seen in C3-KO mice couldn’t be found in MBL-KO mice. Thus the activation of the complement system in ventricular remodelling is not related to the MBL-pathway.
KW  - Chronische Herzinsuffizienz
KW  - Komplement <Immunologie>
KW  - Herzinfarkt
KW  - myocardial infarction
KW  - heart failure
KW  - complement system
Y1  - 2010
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-55521
ER  - 
TY  - JOUR
A1  - Traub, Jan
A1  - Otto, Markus
A1  - Sell, Roxane
A1  - Göpfert, Dennis
A1  - Homola, György
A1  - Steinacker, Petra
A1  - Oeckl, Patrick
A1  - Morbach, Caroline
A1  - Frantz, Stefan
A1  - Pham, Mirko
A1  - Störk, Stefan
A1  - Stoll, Guido
A1  - Frey, Anna
T1  - Serum phosphorylated tau protein 181 and neurofilament light chain in cognitively impaired heart failure patients
JF  - Alzheimer's Research & Therapy
N2  - Background
Chronic heart failure (HF) is known to increase the risk of developing Alzheimer’s dementia significantly. Thus, detecting and preventing mild cognitive impairment, which is common in patients with HF, is of great importance. Serum biomarkers are increasingly used in neurological disorders for diagnostics, monitoring, and prognostication of disease course. It remains unclear if neuronal biomarkers may help detect cognitive impairment in this high-risk population. Also, the influence of chronic HF and concomitant renal dysfunction on these biomarkers is not well understood.

Methods
Within the monocentric Cognition.Matters-HF study, we quantified the serum levels of phosphorylated tau protein 181 (pTau) and neurofilament light chain (NfL) of 146 extensively phenotyped chronic heart failure patients (aged 32 to 85 years; 15.1% women) using ultrasensitive bead-based single-molecule immunoassays. The clinical work-up included advanced cognitive testing and cerebral magnetic resonance imaging (MRI).

Results
Serum concentrations of NfL ranged from 5.4 to 215.0 pg/ml (median 26.4 pg/ml) and of pTau from 0.51 to 9.22 pg/ml (median 1.57 pg/ml). We detected mild cognitive impairment (i.e., T-score < 40 in at least one cognitive domain) in 60% of heart failure patients. pTau (p = 0.014), but not NfL, was elevated in this group. Both NfL (ρ = − 0.21; p = 0.013) and pTau (ρ = − 0.25; p = 0.002) related to the cognitive domain visual/verbal memory, as well as white matter hyperintensity volume and cerebral and hippocampal atrophy. In multivariable analysis, both biomarkers were independently influenced by age (T = 4.6 for pTau; T = 5.9 for NfL) and glomerular filtration rate (T = − 2.4 for pTau; T = − 3.4 for NfL). Markers of chronic heart failure, left atrial volume index (T = 4.6) and NT-proBNP (T = 2.8), were further cardiological determinants of pTau and NfL, respectively. In addition, pTau was also strongly affected by serum creatine kinase levels (T = 6.5) and ferritin (T = − 3.1).

Conclusions
pTau and NfL serum levels are strongly influenced by age-dependent renal and cardiac dysfunction. These findings point towards the need for longitudinal examinations and consideration of frequent comorbidities when using neuronal serum biomarkers.
KW  - Alzheimer’s dementia
KW  - heart failure
KW  - cognitive impairment
KW  - neurofilament light chain
KW  - phosphorylated tau protein
KW  - renal function
KW  - age
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300515
VL  - 14
ER  - 
TY  - JOUR
A1  - Traub, Jan
A1  - Frey, Anna
A1  - Störk, Stefan
T1  - Chronic neuroinflammation and cognitive decline in patients with cardiac disease: evidence, relevance, and therapeutic implications
JF  - Life
N2  - Acute and chronic cardiac disorders predispose to alterations in cognitive performance, ranging from mild cognitive impairment to overt dementia. Although this association is well-established, the factors inducing and accelerating cognitive decline beyond ageing and the intricate causal pathways and multilateral interdependencies involved remain poorly understood. Dysregulated and persistent inflammatory processes have been implicated as potentially causal mediators of the adverse consequences on brain function in patients with cardiac disease. Recent advances in positron emission tomography disclosed an enhanced level of neuroinflammation of cortical and subcortical brain regions as an important correlate of altered cognition in these patients. In preclinical and clinical investigations, the thereby involved domains and cell types of the brain are gradually better characterized. Microglia, resident myeloid cells of the central nervous system, appear to be of particular importance, as they are extremely sensitive to even subtle pathological alterations affecting their complex interplay with neighboring astrocytes, oligodendrocytes, infiltrating myeloid cells, and lymphocytes. Here, we review the current evidence linking cognitive impairment and chronic neuroinflammation in patients with various selected cardiac disorders including the aspect of chronic neuroinflammation as a potentially druggable target.
KW  - neuroinflammation
KW  - cognitive impairment
KW  - dementia
KW  - myocardial infarction
KW  - heart failure
KW  - hypertension
KW  - coronary artery disease
KW  - atrial fibrillation
KW  - cardiac arrest
KW  - aortic valve stenosis
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304869
SN  - 2075-1729
VL  - 13
IS  - 2
ER  - 
TY  - JOUR
A1  - Störk, Stefan
A1  - Bernhardt, Alexandra
A1  - Böhm, Michael
A1  - Brachmann, Johannes
A1  - Dagres, Nikolaos
A1  - Frantz, Stefan
A1  - Hindricks, Gerd
A1  - Köhler, Friedrich
A1  - Zeymer, Uwe
A1  - Rosenkranz, Stephan
A1  - Angermann, Christiane
A1  - Aßmus, Birgit
T1  - Pulmonary artery sensor system pressure monitoring to improve heart failure outcomes (PASSPORT-HF): rationale and design of the PASSPORT-HF multicenter randomized clinical trial
JF  - Clinical Research in Cardiology
N2  - Background
Remote monitoring of patients with New York Heart Association (NYHA) functional class III heart failure (HF) using daily transmission of pulmonary artery (PA) pressure values has shown a reduction in HF-related hospitalizations and improved quality of life in patients.

Objectives
PASSPORT-HF is a prospective, randomized, open, multicenter trial evaluating the effects of a hemodynamic-guided, HF nurse-led care approach using the CardioMEMS™ HF-System on clinical end points.

Methods and results
The PASSPORT-HF trial has been commissioned by the German Federal Joint Committee (G-BA) to ascertain the efficacy of PA pressure-guided remote care in the German health-care system. PASSPORT-HF includes adult HF patients in NYHA functional class III, who experienced an HF-related hospitalization within the last 12 months. Patients with reduced ejection fraction must be on stable guideline-directed pharmacotherapy. Patients will be randomized centrally 1:1 to implantation of a CardioMEMS™ sensor or control. All patients will receive post-discharge support facilitated by trained HF nurses providing structured telephone-based care. The trial will enroll 554 patients at about 50 study sites. The primary end point is a composite of the number of unplanned HF-related rehospitalizations or all-cause death after 12 months of follow-up, and all events will be adjudicated centrally. Secondary end points include device/system-related complications, components of the primary end point, days alive and out of hospital, disease-specific and generic health-related quality of life including their sub-scales, and laboratory parameters of organ damage and disease progression.

Conclusions
PASSPORT-HF will define the efficacy of implementing hemodynamic monitoring as a novel disease management tool in routine outpatient care.

Trial registration
ClinicalTrials.gov; NCT04398654, 13-MAY-2020.
KW  - heart failure
KW  - pulmonary artery pressure
KW  - remote monitoring
KW  - CardioMEMS™ HF-System
KW  - randomized controlled trial
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324026
VL  - 111
IS  - 11
ER  - 
TY  - JOUR
A1  - Steinhardt, Maximilian J.
A1  - Cejka, Vladimir
A1  - Chen, Mengmeng
A1  - Bäuerlein, Sabrina
A1  - Schäfer, Julia
A1  - Adrah, Ali
A1  - Ihne-Schubert, Sandra M.
A1  - Papagianni, Aikaterini
A1  - Kortüm, K. Martin
A1  - Morbach, Caroline
A1  - Störk, Stefan
T1  - Safety and tolerability of SGLT2 inhibitors in cardiac amyloidosis — a clinical feasibility study
JF  - Journal of Clinical Medicine
N2  - Sodium-glucose transport protein 2 inhibitors (SGLT2i) slow the progression of renal dysfunction and improve the prognosis of patients with heart failure. Amyloidosis constitutes an important subgroup for which evidence is lacking. Amyloidotic fibrils originating from misfolded transthyretin and light chains are the causal agents in ATTR and AL amyloidosis. In these most frequent subtypes, cardiac involvement is the most common organ manifestation. Because cardiac and renal function frequently deteriorate over time, even under best available treatment, SGLT2i emerge as a promising treatment option due to their reno- and cardioprotective properties. We retrospectively analyzed patients with cardiac amyloidosis, who received either dapagliflozin or empagliflozin. Out of 79 patients, 5.1% had urinary tract infections; 2 stopped SGLT2i therapy; and 2.5% died unrelated to the intake of SGLT2i. No genital mycotic infections were observed. As expected, a slight drop in the glomerular filtration rate was noted, while the NYHA functional status, cardiac and hepatic function, as well as the 6 min walk distance remained stable over time. These data provide a rationale for the use of SGLT2i in patients with amyloidosis and concomitant cardiac or renal dysfunction. Prospective randomized data are desired to confirm safety and to prove efficacy in this increasingly important group of patients.
KW  - heart failure
KW  - chronic kidney disease
KW  - amyloidosis
KW  - SGLT2 inhibitors
Y1  - 2024
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-356024
SN  - 2077-0383
VL  - 13
IS  - 1
ER  - 
TY  - JOUR
A1  - Sommer, Kim K.
A1  - Amr, Ali
A1  - Bavendiek, Udo
A1  - Beierle, Felix
A1  - Brunecker, Peter
A1  - Dathe, Henning
A1  - Eils, Jürgen
A1  - Ertl, Maximilian
A1  - Fette, Georg
A1  - Gietzelt, Matthias
A1  - Heidecker, Bettina
A1  - Hellenkamp, Kristian
A1  - Heuschmann, Peter
A1  - Hoos, Jennifer D. E.
A1  - Kesztyüs, Tibor
A1  - Kerwagen, Fabian
A1  - Kindermann, Aljoscha
A1  - Krefting, Dagmar
A1  - Landmesser, Ulf
A1  - Marschollek, Michael
A1  - Meder, Benjamin
A1  - Merzweiler, Angela
A1  - Prasser, Fabian
A1  - Pryss, Rüdiger
A1  - Richter, Jendrik
A1  - Schneider, Philipp
A1  - Störk, Stefan
A1  - Dieterich, Christoph
T1  - Structured, harmonized, and interoperable integration of clinical routine data to compute heart failure risk scores
JF  - Life
N2  - Risk prediction in patients with heart failure (HF) is essential to improve the tailoring of preventive, diagnostic, and therapeutic strategies for the individual patient, and effectively use health care resources. Risk scores derived from controlled clinical studies can be used to calculate the risk of mortality and HF hospitalizations. However, these scores are poorly implemented into routine care, predominantly because their calculation requires considerable efforts in practice and necessary data often are not available in an interoperable format. In this work, we demonstrate the feasibility of a multi-site solution to derive and calculate two exemplary HF scores from clinical routine data (MAGGIC score with six continuous and eight categorical variables; Barcelona Bio-HF score with five continuous and six categorical variables). Within HiGHmed, a German Medical Informatics Initiative consortium, we implemented an interoperable solution, collecting a harmonized HF-phenotypic core data set (CDS) within the openEHR framework. Our approach minimizes the need for manual data entry by automatically retrieving data from primary systems. We show, across five participating medical centers, that the implemented structures to execute dedicated data queries, followed by harmonized data processing and score calculation, work well in practice. In summary, we demonstrated the feasibility of clinical routine data usage across multiple partner sites to compute HF risk scores. This solution can be extended to a large spectrum of applications in clinical care.
KW  - medical informatics initiative
KW  - HiGHmed
KW  - medical data integration center
KW  - clinical routine data
KW  - heart failure
KW  - risk prediction scores
KW  - semantic interoperability
KW  - openEHR
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-275239
SN  - 2075-1729
VL  - 12
IS  - 5
ER  - 
TY  - THES
A1  - Schöpp, Corinna
T1  - Die Wirkung von Fractalkine auf Thrombozytenaktivierung und Endotheldysfunktion bei Herzinsuffizienz und Diabetes
T1  - Influence of fractalkine on platelet activation and endothelial dysfunction in heart failure and diabetes
N2  - Diabetes mellitus und Herzinsuffizienz gehen mit einer stark erhöhten kardiovaskulären Morbidität einher. Bei beiden Krankheiten besteht eine Endotheldysfunktion und eine verstärkte Thrombozytenaktivierung. Daraus resultieren wiederum frühe atherosklerotische Läsionen bzw. eine Progression der Herzinsuffizienz. Das Chemokin Fractalkine wurde als Risikofaktor für eine schwere koronare Herzerkrankung beschrieben. Der Fractalkine-Rezeptor ist mit einem erhöhten Atherosklerose-Risiko assoziiert. Auch ist Fractalkine in der Lage, eine Endotheldysfunktion sowie eine Thrombozytenaktivierung zu induzieren bzw. zu verstärken. Es lag daher nahe, den Effekt von Fractalkine auf Endothel und Thrombozyten von Ratten mit Herzinsuffizienz und Diabetes mellitus zu untersuchen. Die Expression von Fractalkine wie auch seines Rezeptors war in der Aorta bei Herzinsuffizienz und Diabetes mellitus gesteigert. Auch das lösliche Fractalkine im Serum war bei beiden Krankheitsmodellen erhöht. Auf der Thrombozytenoberfläche zeigte sich eine stärkere Fractalkine-Rezeptor-Expression. Durch Stimulation mit Fractalkine konnte bei beiden Modellen eine signifikant akzelerierte Thrombozytenaktivierung erzielt werden. Bei den herzinsuffizienten Tieren zeigte sich eine signifikante Verschlechterung der schon bestehenden endothelialen Dysfunktion nach Inkubation mit Fractalkine. Deshalb kann man davon ausgehen, dass Fractalkine eine bedeutende Rolle sowohl für die Atherosklerose bei Diabetes mellitus als auch bei Herzinsuffizienz spielt. Man könnte sich nun Fractalkine und seinen Rezeptor als einen neuen therapeutischen Ansatzpunkt für die Verhinderung der Progression sowohl atherosklerotischer Läsionen als auch der Inflammation bei Herzinsuffizienz vorstellen. Dadurch wäre eine Reduzierung weiterer atherosklerotischer Komplikationen wie Myokardinfarkt oder Schlaganfall eventuell möglich.
N2  - Diabetes mellitus and congestive heart failure are associated with increased cardiovascular morbidity and mortality. Both diseases display endothelial dysfunction and increased platelet activation resulting in early atherosclerotic lesion development or progression of heart failure. The chemokine fractalkine has been described as a risk factor for severe coronary artery disease. The fractalkine-receptor is associated with enhanced probability for atherosclerosis. Furthermore, fractalkine is able to induce endothelial dysfunction and to aggravate platelet activiation. Therefore, the effect of fractalkine on endothelium and platelets was investigated in rats with heart failure and diabetes mellitus. The expression of fractalkine itself as well as of its receptor was increased in rat aorta during heart failure and diabetes. Although, soluble fractalkine serum levels were increased in both disease models. Fractalkine-receptor expression on the platelet surface was strongly enhanced in both models. Stimulating platelets from these disease models with fractalkine resulted in significant enhancement of platelet activation. In animals with congestive heart failure, incubation with fractalkine induced a significant deterioration of the preexisting endothelial dysfunction. Therefore, it has to be assumed, that fractalkine is a central regulator for atherosclerosis in diabetes and in heart failure. Fractalkine as well as its receptor might be useful as a novel therapeutic target to prevent atherosclerotic lesion progression in diabetes or inflammation in heart failure. This could potentially further reduce atherosclerotic complications such as myocardial infarction or stroke.
KW  - Arteriosklerose
KW  - Fractalkine
KW  - Herzinsuffizienz
KW  - Diabetes mellitus
KW  - Endotheldysfunktion
KW  - Thrombozytenaktivierung
KW  - Fractalkine
KW  - heart failure
KW  - diabetes melitus
KW  - endothelial dysfunction
KW  - platelet activation
Y1  - 2009
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-43371
ER  - 
TY  - JOUR
A1  - Morbach, Caroline
A1  - Wagner, Martin
A1  - Güntner, Stefan
A1  - Malsch, Carolin
A1  - Oezkur, Mehmet
A1  - Wood, David
A1  - Kotseva, Kornelia
A1  - Leyh, Rainer
A1  - Ertl, Georg
A1  - Karmann, Wolfgang
A1  - Heuschmann, Peter U
A1  - Störk, Stefan
T1  - Heart failure in patients with coronary heart disease: Prevalence, characteristics and guideline implementation - Results from the German EuroAspire IV cohort
JF  - BMC Cardiovascular Disorders
N2  - Background:
Adherence to pharmacotherapeutic treatment guidelines in patients with heart failure (HF) is of major prognostic importance, but thorough implementation of guidelines in routine care remains insufficient. Our aim was to investigate prevalence and characteristics of HF in patients with coronary heart disease (CHD), and to assess the adherence to current HF guidelines in patients with HF stage C, thus identifying potential targets for the optimization of guideline implementation.
Methods:
Patients from the German sample of the European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EuroAspire) IV survey with a hospitalization for CHD within the previous six to 36 months providing valid data on echocardiography as well as on signs and symptoms of HF were categorized into stages of HF: A, prevalence of risk factors for developing HF; B, asymptomatic but with structural heart disease; C, symptomatic HF. A Guideline Adherence Indicator (GAI-3) was calculated for patients with reduced (≤40%) left ventricular ejection fraction (HFrEF) as number of drugs taken per number of drugs indicated; beta-blockers, angiotensin converting enzyme inhibitors/angiotensin receptor blockers, and mineralocorticoid receptor antagonists (MRA) were considered.
Results:
509/536 patients entered analysis. HF stage A was prevalent in n = 20 (3.9%), stage B in n = 264 (51.9%), and stage C in n = 225 (44.2%) patients; 94/225 patients were diagnosed with HFrEF (42%). Stage C patients were older, had a longer duration of CHD, and a higher prevalence of arterial hypertension. Awareness of pre-diagnosed HF was low (19%). Overall GAI-3 of HFrEF patients was 96.4% with a trend towards lower GAI-3 in patients with lower LVEF due to less thorough MRA prescription.
Conclusions:
In our sample of CHD patients, prevalence of HF stage C was high and a sizable subgroup suffered from HFrEF. Overall, pharmacotherapy was fairly well implemented in HFrEF patients, although somewhat worse in patients with more reduced ejection fraction. Two major targets were identified possibly suited to further improve the implementation of HF guidelines: 1) increase patients´ awareness of diagnosis and importance of HF; and 2) disseminate knowledge about the importance of appropriately implementing the use of mineralocorticoid receptor antagonists.
Trial registration: 
This is a cross-sectional analysis of a non-interventional study. Therefore, it was not registered as an interventional trial.
KW  - awareness
KW  - heart failure
KW  - pharmacotherapy
KW  - coronary artery disease
KW  - coronary heart disease
KW  - euroaspire
KW  - guideline adherence
KW  - guideline implementation
KW  - mineralocorticoid antagonist
KW  - preserved ejection fraction
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157738
VL  - 17
IS  - 108
ER  - 
TY  - JOUR
A1  - Montellano, Felipe A.
A1  - Kluter, Elisabeth J.
A1  - Rücker, Viktoria
A1  - Ungethüm, Kathrin
A1  - Mackenrodt, Daniel
A1  - Wiedmann, Silke
A1  - Dege, Tassilo
A1  - Quilitzsch, Anika
A1  - Morbach, Caroline
A1  - Frantz, Stefan
A1  - Störk, Stefan
A1  - Haeusler, Karl Georg
A1  - Kleinschnitz, Christoph
A1  - Heuschmann, Peter U.
T1  - Cardiac dysfunction and high-sensitive C-reactive protein are associated with troponin T elevation in ischemic stroke: insights from the SICFAIL study
JF  - BMC Neurology
N2  - Background
Troponin elevation is common in ischemic stroke (IS) patients. The pathomechanisms involved are incompletely understood and comprise coronary and non-coronary causes, e.g. autonomic dysfunction. We investigated determinants of troponin elevation in acute IS patients including markers of autonomic dysfunction, assessed by heart rate variability (HRV) time domain variables.
Methods
Data were collected within the Stroke Induced Cardiac FAILure (SICFAIL) cohort study. IS patients admitted to the Department of Neurology, Würzburg University Hospital, underwent baseline investigation including cardiac history, physical examination, echocardiography, and blood sampling. Four HRV time domain variables were calculated in patients undergoing electrocardiographic Holter monitoring. Multivariable logistic regression with corresponding odds ratios (OR) and 95% confidence intervals (CI) was used to investigate the determinants of high-sensitive troponin T (hs-TnT) levels ≥14 ng/L.
Results
We report results from 543 IS patients recruited between 01/2014–02/2017. Of those, 203 (37%) had hs-TnT ≥14 ng/L, which was independently associated with older age (OR per year 1.05; 95% CI 1.02–1.08), male sex (OR 2.65; 95% CI 1.54–4.58), decreasing estimated glomerular filtration rate (OR per 10 mL/min/1.73 m2 0.71; 95% CI 0.61–0.84), systolic dysfunction (OR 2.79; 95% CI 1.22–6.37), diastolic dysfunction (OR 2.29; 95% CI 1.29–4.02), atrial fibrillation (OR 2.30; 95% CI 1.25–4.23), and increasing levels of C-reactive protein (OR 1.48 per log unit; 95% CI 1.22–1.79). We did not identify an independent association of troponin elevation with the investigated HRV variables.
Conclusion
Cardiac dysfunction and elevated C-reactive protein, but not a reduced HRV as surrogate of autonomic dysfunction, were associated with increased hs-TnT levels in IS patients independent of established cardiovascular risk factors.
KW  - echocardiography
KW  - ischemic stroke
KW  - troponin
KW  - heart failure
KW  - biomarkers
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300119
VL  - 22
IS  - 1
ER  - 
TY  - THES
A1  - Lau, Kolja
T1  - Diastolische Herzfunktion und ihre Vorhersagekraft auf das Langzeitüberleben bei HerzinsuffizienzpatientInnen mit mittelgradiger oder reduzierter linksventrikulärer Ejektionsfraktion
T1  - Impact of diastolic dysfunction on outcome in heart failure patients with mid-range or reduced ejection fraction
N2  - Diese retrospektive Auswertung von PatientInnendaten der kardiologischen Ambulanz des Universitätsklinikums Würzburg konnte zeigen, dass die Bestimmung der diastolischen Dysfunktion prognostisch relevante Informationen enthält. Das Studienkollektiv wurde anhand der gemessenen Ejektionsfraktion in die zwei Untersuchungsgruppen HFrEF und HFmrEF eingeteilt. Diese zwei Untersuchungsgruppen wurden anhand ihrer klinisch und echokardiographisch bestimmten Charakteristika verglichen. Anschließend wurden drei diastolische Parameter (E/e’, LAVi und TRVmax) auf ihre prognostische Relevanz untersucht. Die abschließende Untersuchung gruppierte die PatientInnen anhand der Schwere ihrer diastolischen Dysfunktion (mild / moderat / schwer) und untersuchte ebenfalls das Langzeitüberleben.

Die HFmrEF-Gruppe zeigte ähnliche klinische Charakteristika wie die HFrEF-Gruppe. Eine ischämische Genese der Herzinsuffizienz wurde in der HFmrEF-Gruppe im Vergleich zur HFrEF-Gruppe häufiger beobachtet.
Die Überlebenszeitanalysen konnten bei PatientInnen in der HFmrEF-Gruppe zeigen, dass ein dilatierter linker Vorhof (LAVi) oder eine große Regurgitation über der Trikuspidalklappe (TRVmax) mit einer schlechten Prognose einhergehen. Bei HFrEF-PatientInnen hingegen konnte dies nicht nachgewiesen werden. Hier zeigte sich, dass insbesondere der Parameter E/e’septal prognostisch relevante Informationen enthält.
Die Auswertung der Untersuchungsgruppen nach Einteilung anhand der Schwere der diastolischen Dysfunktion konnte die gefunden Effekte bestätigen. Eine moderate bis schwere diastolische Dysfunktion war mit einer signifikant schlechteren Prognose behaftet, und zwar sowohl in der HFrEF- wie auch in der HFmrEF-Gruppe.

Die gefunden Ergebnisse zeigen, dass die diastolische Dysfunktion auch bei PatientInnen mit einer systolischen Herzinsuffizienz wichtige prognostische Informationen enthalten. In der klinischen Routine sollte die echokardiographische Bestimmung der diastolischen Herzfunktion standardmäßig durchgeführt werden.
Die Ergebnisse könnten nicht nur in der Diagnostik zur Kategorisierung der PatientInnen und Bestimmung der Prognose, sondern auch hinsichtlich der Therapie von großem zukünftigem Nutzen sein. Hierzu sollten perspektivisch vor allem therapeutische Aspekte in prospektiven, idealerweise randomisierten Studien untersucht werden, welche sich auf die Erkenntnisse dieser Arbeit beziehen.
N2  - This study evaluated the echocardiographic measured diastolic dysfunction in heart failure patients with mid-range or reduced left ventricular ejection fraction.
Conclusions:
We could demonstrate, that moderate to severe diastolic dysfunction identified by echocardiography is significantly associated with all-cause mortality both in patients with HFrEF and HFmrEF. Septal E/E' ratio serves es an independent determinant of all-cause mortality in patients with HFrEF but not in patients with HFmrEF. LAVi and TRVmax could be useful as an independent determinant of all-cause mortality in patients with HFmrEF.
KW  - Herzinsuffizienz
KW  - Transthorakale Echokardiographie
KW  - heart failure
KW  - HFrEF
KW  - HFmrEF
KW  - diagnostic
KW  - prognostic
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241704
ER  - 
TY  - THES
A1  - Langguth, Jan-Philipp
T1  - Prädiktoren der generischen und krankheitsspezifischen Lebensqualität bei Patienten mit chronischer Herzinsuffizienz
T1  - Predictors of generic and disease-specific health-related quality of life in patients with chronic systolic heart failure
N2  - No abstract available
KW  - Lebensqualität
KW  - Herzinsuffizienz
KW  - Depression
KW  - Prädiktoren
KW  - Lebensqualitätsfragebögen
KW  - heart failure
KW  - health related quality of life
KW  - depression
KW  - predictors
Y1  - 2009
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-37153
ER  - 
TY  - THES
A1  - Langer, Simon
T1  - Herz-Hirn Interaktion im Mausmodell: Herzinsuffizienz nach Myokardinfarkt führt zu depressivem Verhalten bei Mäusen
T1  - Heart & Brain interactions in mice: chronic heart failure after myocardial infarction leads to depressive behaviour in mice
N2  - Herzinsuffizienz, Depression und Angststörungen treten gehäuft gemeinsam auf und beeinflussen teilweise gegenseitig ihre Prognose. Die Zusammenhänge zwischen diesen Erkrankungen sind bislang nicht aufgeklärt.
In der vorliegenden Arbeit führte ischämische Herzinsuffizienz im Mausmodell zu Depressions-ähnlichem Verhalten innerhalb von 8 Wochen nach Infarktinduktion. Weiter zeigte sich eine Minderung der Gedächtnisleistung. Angst-assoziiertes Verhalten ließ sich nicht nachweisen. Immunhistochemisch konnten keine Veränderungen in spezifischen Hirnarealen nachgewiesen werden. Molekulare Methoden legen Veränderungen des Serotoninstoffwechsels als mögliche Erklärung nahe.
Nach operativer Ligatur eines Herzkrankgefäßes wurden C57/Bl6N Mäuse über einen Zeitraum von 8 Wochen beobachtet. In dieser Zeit wurden neben Herzultraschalluntersuchungen eine Reihe von Verhaltenstest durchgeführt, um depressive und ängstliche Verhaltensstrukturen sowie die kognitive Leistungsfähigkeit beurteilen zu können. Nach Ablauf des Beobachtungszeitraumes wurden das Herz und das Gehirn entnommen und weiteren histologischen und molekularen Untersuchungen zugeführt.
Die histologische Aufarbeitung des Herzens nach Ende des Versuchszeitraumes bestätigte die Beobachtungen anderen Autoren, dass eine Infarktgröße von mehr als 30% mit sehr hoher Wahrscheinlichkeit zur Entstehung einer Herzinsuffizienz führt.
Im der histologischen Aufarbeitung des Gehirns zeigen sich keine strukturellen Veränderungen bei herzkranken Mäusen, die die beobachteten Änderungen im Verhalten begründen könnten. Insbesondere kann eine hypoxische Hirnschädigung durch eine etwaige Minderperfusion empfindlicher Hirnareale ausgeschlossen werden.
Mäuse, die nach Induktion eines Myokardinfarktes eine Herzinsuffizienz entwickeln, zeigen nach 8 Wochen Depressions-assoziiertes, adynamisches Verhalten sowie eine Verminderung der kognitiven Leistungsfähigkeit, nicht aber Anzeichen von Angststörungen. Diesen Verhaltensänderungen kann kein strukturelles Korrelat im Gehirn zugewiesen werden. Dies ist ein Indiz dafür, dass sich Veränderung auf molekularer Ebene vollziehen, welche sich dem Mikroskop entziehen. Die im Myokard beobachtete Regulation des Serotoninstoffwechsels ist ein möglicher Erklärungsansatz hierfür.
N2  - Chronic heart failure and depression are common comorbidities, that also have influence on the overall prognosis. The pathomechanisms of these illnesses remain still to be uncovered. 
In this experiment, we investigated mice with chronic heart failure after myocardial infarction over a period of 8 weeks. Male C57/Bl6N mice underwent ligation of the left anterior descending coronary artery. Heart failure was both confirmed by echocardiography and post-mortem. Sham-operated mice without ligation were used as control group.
We discovered that these mice developed behavioral signs of depression in multiple behavioral testing. Also, we found signs for cognitive impairment in the object recognition task. No signs of increased anxiety was found.
The hippocampal brain region is associated with the genesis of behaviour. Immunohistochemistry of the brain showed no morphological changes in this distinct area. 
We found increased expression of genes connected to the serotonine pathway in mice suffering from chronic heart failure, suggesting a possible pathomechanism for the shown behavioral changes.
KW  - Deutsches Zentrum für Herzinsuffizienz Würzburg
KW  - Herzinsuffizienz
KW  - Depression
KW  - Herzinsuffizienz
KW  - Depression
KW  - Verhalten
KW  - heart failure
KW  - behavioral changes
KW  - depression
KW  - C57/Bl6
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-154733
ER  - 
TY  - JOUR
A1  - Kerwagen, Fabian
A1  - Riemer, Uwe
A1  - Wachter, Rolf
A1  - von Haehling, Stephan
A1  - Abdin, Amr
A1  - Böhm, Michael
A1  - Schulz, Martin
A1  - Störk, Stefan
T1  - Impact of the COVID-19 pandemic on implementation of novel guideline-directed medical therapies for heart failure in Germany: a nationwide retrospective analysis
JF  - The Lancet Regional Health - Europe
N2  - Background
Guideline-directed medical therapy (GDMT) is the cornerstone in the treatment of patients with heart failure and reduced ejection fraction (HFrEF) and novel substances such as sacubitril/valsartan (S/V) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) have demonstrated marked clinical benefits. We investigated their implementation into real-world HF care in Germany before, during, and after the COVID-19 pandemic period.

Methods
The IQVIA LRx data set is based on ∼80% of 73 million people covered by the German statutory health insurance. Prescriptions of S/V were used as a proxy for HFrEF. Time trends were analysed between Q1/2016 and Q2/2023 for prescriptions for S/V alone and in combination therapy with SGLT2i.

Findings
The number of patients treated with S/V increased from 5260 in Q1/2016 to 351,262 in Q2/2023. The share of patients with combination therapy grew from 0.6% (29 of 5260) to 14.2% (31,128 of 219,762) in Q2/2021, and then showed a steep surge up to 54.8% (192,429 of 351,262) in Q2/2023, coinciding with the release of the European Society of Cardiology (ESC) guidelines for HF in Q3/2021. Women and patients aged >80 years were treated less often with combined therapy than men and younger patients. With the start of the COVID-19 pandemic, the number of patients with new S/V prescriptions dropped by 17.5% within one quarter, i.e., from 26,855 in Q1/2020 to 22,145 in Q2/2020, and returned to pre-pandemic levels only in Q1/2021.

Interpretation
The COVID-19 pandemic was associated with a 12-month deceleration of S/V uptake in Germany. Following the release of the ESC HF guidelines, the combined prescription of S/V and SGLT2i was readily adopted. Further efforts are needed to fully implement GDMT and strengthen the resilience of healthcare systems during public health crises.
KW  - health policy
KW  - oncology
KW  - internal medicine
KW  - heart failure
KW  - COVID-19
KW  - sacubitril-valsartan
KW  - sodium-glucose co-transporter-2 inhibitors
KW  - guideline-directed medical therapy
KW  - evidence-based practice
KW  - real-world
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-350510
SN  - 2666-7762
VL  - 35
ER  - 
TY  - JOUR
A1  - Hofmann, Ulrich
A1  - Frantz, Stefan
T1  - How can we cure a heart "in flame"? A translational view on inflammation in heart failure
JF  - Basic Research in Cardiology
N2  - The prevalence of chronic heart failure is still increasing making it a major health issue in the 21st century. Tremendous evidence has emerged over the past decades that heart failure is associated with a wide array of mechanisms subsumed under the term "inflammation". Based on the great success of immuno-suppressive treatments in auto-immunity and transplantation, clinical trials were launched targeting inflammatory mediators in patients with chronic heart failure. However, they widely lacked positive outcomes. The failure of the initial study program directed against tumor necrosis factor-a led to the search for alternative therapeutic targets involving a broader spectrum of mechanisms besides cytokines. We here provide an overview of the current knowledge on immune activation in chronic heart failure of different etiologies, summarize clinical studies in the field, address unresolved key questions, and highlight some promising novel therapeutic targets for clinical trials from a translational basic science and clinical perspective.
KW  - cytokines
KW  - immuno-modulation
KW  - heart failure
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134497
VL  - 108
IS  - 356
ER  - 
TY  - JOUR
A1  - Henneges, Carsten
A1  - Morbach, Caroline
A1  - Sahiti, Floran
A1  - Scholz, Nina
A1  - Frantz, Stefan
A1  - Ertl, Georg
A1  - Angermann, Christiane E.
A1  - Störk, Stefan
T1  - Sex-specific bimodal clustering of left ventricular ejection fraction in patients with acute heart failure
JF  - ESH Heart Failure
N2  - Aims
There is an ongoing discussion whether the categorization of patients with heart failure according to left ventricular ejection fraction (LVEF) is scientifically justified and clinically relevant. Major efforts are directed towards the identification of appropriate cut-off values to correctly allocate heart failure-specific pharmacotherapy. Alternatively, an LVEF continuum without definite subgroups is discussed. This study aimed to evaluate the natural distribution of LVEF in patients presenting with acutely decompensated heart failure and to identify potential subgroups of LVEF in male and female patients.

Methods and results
We identified 470 patients (mean age 75 ± 11 years, n = 137 female) hospitalized for acute heart failure in whom LVEF could be quantified by Simpson's method in an in-hospital echocardiogram. Non-parametric modelling revealed a bimodal shape of the LVEF distribution. Parametric modelling identified two clusters suggesting two LVEF peaks with mean (variance) of 61% (9%) and 31% (10%), respectively. Sub-differentiation by sex revealed a sex-specific bimodal clustering of LVEF. The respective threshold differentiating between ‘high’ and ‘low’ LVEF was 45% in men and 52% in women.

Conclusions
In patients presenting with acute heart failure, LVEF clustered in two subgroups and exhibited profound sex-specific distributional differences. These findings might enrich the scientific process to identify distinct subgroups of heart failure patients, which might each benefit from respectively tailored (pharmaco)therapies.
KW  - heart failure
KW  - left ventricular ejection fraction
KW  - sex differences
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265839
VL  - 9
IS  - 1
ER  - 
TY  - JOUR
A1  - Güder, Gülmisal
A1  - Wilkesmann, Joana
A1  - Scholz, Nina
A1  - Leppich, Robert
A1  - Düking, Peter
A1  - Sperlich, Billy
A1  - Rost, Christian
A1  - Frantz, Stefan
A1  - Morbach, Caroline
A1  - Sahiti, Floran
A1  - Stefenelli, Ulrich
A1  - Breunig, Margret
A1  - Störk, Stefan
T1  - Establishing a cardiac training group for patients with heart failure: the "HIP-in-Würzburg" study
JF  - Clinical Research in Cardiology
N2  - Background
Exercise training in heart failure (HF) is recommended but not routinely offered, because of logistic and safety-related reasons. In 2020, the German Society for Prevention&Rehabilitation and the German Society for Cardiology requested establishing dedicated ""HF training groups."" Here, we aimed to implement and evaluate the feasibility and safety of one of the first HF training groups in Germany.
Methods
Twelve patients (three women) with symptomatic HF (NYHA class II/III) and an ejection fraction ≤ 45% participated and were offered weekly, physician-supervised exercise training for 1 year. Patients received a wrist-worn pedometer (M430 Polar) and underwent the following assessments at baseline and after 4, 8 and 12 months: cardiopulmonary exercise test, 6-min walk test, echocardiography (blinded reading), and quality of life assessment (Kansas City Cardiomyopathy Questionnaire, KCCQ).
Results
All patients (median age [quartiles] 64 [49; 64] years) completed the study and participated in 76% of the offered 36 training sessions. The pedometer was worn ≥ 1000 min per day over 86% of the time. No cardiovascular events occurred during training. Across 12 months, NT-proBNP dropped from 986 pg/ml [455; 1937] to 483 pg/ml [247; 2322], and LVEF increased from 36% [29;41] to 41% [32;46]%, (p for trend = 0.01). We observed no changes in exercise capacity except for a subtle increase in peak VO2% predicted, from 66.5 [49; 77] to 67 [52; 78]; p for trend = 0.03. The physical function and social limitation domains of the KCCQ improved from 60 [54; 82] to 71 [58; 95, and from 63 [39; 83] to 78 [64; 92]; p for trend = 0.04 and = 0.01, respectively. Positive trends were further seen for the clinical and overall summary scores.
Conclusion
This pilot study showed that the implementation of a supervised HF-exercise program is feasible, safe, and has the potential to improve both quality of life and surrogate markers of HF severity. This first exercise experiment should facilitate the design of risk-adopted training programs for patients with HF.
KW  - m exercise training
KW  - heart failure
KW  - cardiac training group
KW  - heart failure training group
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-266678
SN  - 1861-0692
VL  - 111
ER  - 
TY  - JOUR
A1  - Gerhardt, Louisa M. S.
A1  - Kordsmeyer, Maren
A1  - Sehner, Susanne
A1  - Güder, Gülmisal
A1  - Störk, Stefan
A1  - Edelmann, Frank
A1  - Wachter, Rolf
A1  - Pankuweit, Sabine
A1  - Prettin, Christiane
A1  - Ertl, Georg
A1  - Wanner, Christoph
A1  - Angermann, Christiane E.
T1  - Prevalence and prognostic impact of chronic kidney disease and anaemia across ACC/AHA precursor and symptomatic heart failure stages
JF  - Clinical Research in Cardiology
N2  - Background
The importance of chronic kidney disease (CKD) and anaemia has not been comprehensively studied in asymptomatic patients at risk for heart failure (HF) versus those with symptomatic HF. We analysed the prevalence, characteristics and prognostic impact of both conditions across American College of Cardiology/American Heart Association (ACC/AHA) precursor and HF stages A–D.

Methods and results
2496 participants from three non-pharmacological German Competence Network HF studies were categorized by ACC/AHA stage; stage C patients were subdivided into C1 and C2 (corresponding to NYHA classes I/II and III, respectively). Overall, patient distribution was 8.1%/35.3%/32.9% and 23.7% in ACC/AHA stages A/B/C1 and C2/D, respectively. These subgroups were stratified by the absence ( – ) or presence ( +) of CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73m2) and anaemia (haemoglobin in women/men < 12/ < 13 g/dL). The primary outcome was all-cause mortality at 5-year follow-up. Prevalence increased across stages A/B/C1 and C2/D (CKD: 22.3%/23.6%/31.6%/54.7%; anaemia: 3.0%/7.9%/21.7%/33.2%, respectively), with concordant decreases in median eGFR and haemoglobin (all p < 0.001). Across all stages, hazard ratios [95% confidence intervals] for all-cause mortality were 2.1 [1.8–2.6] for CKD + , 1.7 [1.4–2.0] for anaemia, and 3.6 [2.9–4.6] for CKD + /anaemia + (all p < 0.001). Population attributable fractions (PAFs) for 5-year mortality related to CKD and/or anaemia were similar across stages A/B, C1 and C2/D (up to 33.4%, 30.8% and 34.7%, respectively).

Conclusions
Prevalence and severity of CKD and anaemia increased across ACC/AHA stages. Both conditions were individually and additively associated with increased 5-year mortality risk, with similar PAFs in asymptomatic patients and those with symptomatic HF.
KW  - anaemia
KW  - ACC/AHA classification
KW  - chronic kidney disease
KW  - comorbidity
KW  - heart failure
KW  - mortality
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-323990
VL  - 112
IS  - 7
ER  - 
TY  - THES
A1  - Fröhlich, Kilian
T1  - Die Komorbidität von chronisch systolischer Herzinsuffizienz und chronisch obstruktiver Atemwegserkrankung: Bedeutung und Konsequenzen unter besonderer Berücksichtigung geschlechtsspezifischer Aspekte
T1  - The comorbidity of chronic heart failure and COPD: Importance, consequences and gender aspects
N2  - Die Prävalenz der chronisch obstruktiven pulmonalen Erkrankung (COPD) bei der systolischen Herzinsuffizienz (HF) wird in der Literatur mit bis zu 20-30% angegeben. Die meisten Publikationen leiteten die Diagnose einer COPD aus anamnestischen Angaben ab, die tatsächliche Prävalenz der spirometrisch bestätigten COPD bei komorbider Herzinsuffizienz war bislang unklar. Ziel der vorliegenden Arbeit war es, die Anteile der Patienten mit anamnestischer COPD sowie mit spirometrisch verifizierter Obstruktiver Ventilationsstörung (OVS) bei einer großen Kohorte von Patienten mit systolischer Herzinsuffizienz zu ermitteln, Charakteristika beider Patientengruppen miteinander zu vergleichen und geschlechtsspezifische Unterschiede aufzudecken. Im Rahmen einer retrospektiven Substudie der INH (Interdisziplinäres Netzwerk Herzinsuffizienz) - Studie wurden Lungenfunktionsanalysen, echokardiographische und anamnestische Befunde von insgesamt 632 Patienten ausgewertet. Die Patienten stellten sich hierzu 6 Monate nach stationärer Behandlung, die aufgrund einer kardialen Dekompensation erfolgt war, in der Herzinsuffizienzambulanz der Universitätsklinik vor. Die Prävalenz der anamnestischen COPD lag in unserem Kollektiv bei 24%. Spirometrisch liess sich eine Obstruktion aber nur bei 16% aller Patienten (98/632) bestätigen. Der positiv prädiktive Wert der anamnestischen COPD zur Vorhersage der spirometrisch bestätigen Atemwegsobstruktion lag mit 0,32 noch unterhalb der zufälligen Ratewahrscheinlichkeit von 0,5. Damit war die anamnestische COPD in 68% der Fälle nicht zutreffend diagnostiziert. Eine COPD konnte zudem bei mehr als der Hälfte aller Patienten mit anamnestischer COPD (83/151, entsprechend 55%), spirometrisch ausgeschlossen werden. Bei Patientinnen mit anamestischer COPD war eine häufigere Einnahme von Schleifendiuretika bei vermehrtem Auftreten klinischer Stauungszeichen zu verzeichnen. Ferner erhielten Frauen (72 vs. 89%, P<0,01), nicht jedoch Männer mit OVS weniger häufig einen Betablocker, was sowohl als Ursache als auch als Konsequenz einer häufigeren (subklinischen) kardialen Dekompensation angesehen werden könnte. Weitere Hinweise darauf, dass v.a. bei Frauen oft keine „echte“, auf Nikotinabusus zurückzuführende COPD vorlag, finden sich bei der Betrachtung des Nichtraucheranteils bei der geschlechtsvergleichenden Analyse Frauen vs. Männer (66,7 vs. 26,5; P<0,01) bzw. bei der Subgruppenanalyse Frauen mit vs. ohne OVS (72,7 vs. 73,5; P=0,57). Die Komorbidität von OVS und Herzinsuffzienz hatte hingegen bei Männern besonders auf die physische Komponente der Lebensqualität negative Auswirkungen (SF 36 Physische Funktion Männer mit vs. ohne OVS 50 vs. 62, P<0,01). In einer Subgruppenanalyse von 278 Patienten, die aufgrund einer kardialen Dekompensation stationär behandelt wurden, und von denen bei 52 denen während des Aufenthaltes spirometrisch eine OVS festgestellt wurde, war die Obstruktion 6 Monate nach Entlassung bei der Hälfte der Patienten nicht mehr nachweisbar. In der multivariaten logistischen Regression waren nur bodyplethysmographischen Parameter wie das Residualvolumen (RLV), das Intrathorakale Gasvolumen (ITGV) und die Totale Lungenkapazität (TLC), nicht jedoch die spirometrischen Messparameter FEV1, FVC und FEV1/FVC prädiktiv für die Persistenz der OVS 6 Monate nach Entlassung. Unsere Daten belegen, dass bei Herzinsuffizienz die anamnestische COPD nur unzureichend mit der spirometrisch nachgewiesenen Obstruktion korreliert. Die COPD bei Herzinsuffizienz wird häufig überschätzt und somit ohne Indikation mit inhalativen Antiobstruktiva therapiert. Auch kommen Betablocker entgegen den Empfehlungen der Leitlinien bei Vorhandensein einer obstruktiven Ventilationsstörung sowie einer Herzinsuffizienz bei Frauen seltener zum Einsatz. Oft ist eine kardiale Stauung und nicht die COPD Ursache einer nachweisbaren Obstruktion. Zur korrekten Diagnose bei OVS und vermuteter kardialer Stauung sind Parameter der Bodyplethysmographie wie das RLV oder ITGV, die bei Erhöhung einen verlässlichen Hinweis auf eine zugrunde liegende COPD liefern, hilfreich. Nach diesen Daten erscheint bei Herzinsuffizienzpatienten mit Verdacht auf eine obstruktive Lungenerkrankung nach bestmöglicher Rekompensation und vor Beginn einer medikamentösen anti-obstruktiven Therapie die Durchführung einer Lungenfunktionsuntersuchung mit Spirometrie und Bodyplethysmographie grundsätzlich indiziert.
N2  - Background: Chronic obstructive pulmonary disease (COPD) is the most common and clinically relevant obstructive ventilatory disorder (OVD). The prevalence of true COPD in heart failure patients is not exactly known, the differential diagnosis may be difficult due to overlapping symptoms. Gender aspects are important in both diseases. This study aimed to evaluate the role and etiology of OVD in patients with chronic systolic HF by assessment of pulmonary function, clinical status and laboratory tests. Methods: 6 months after hospitalization for systolic HF (left ventricular ejection fraction (LVEF) ≤40%) pulmonary function was studied by spirometry in 632 outpatients. A diagnosis of OVD was made if the Tiffeneau ratio was <0.7 (ratio of 1sec-forced expiratory volume and forced vital capacity). A history of ‘COPD’ was assumed if stated in previous medical reports or if patients were on anti-obstructive agents. Results: The prevalence of anamnestic COPD was 24%, but only 16% of the patients had a COPD confirmed by spirometry. Anamnestic COPD was misdiagnosed in 68% of the cases. Patients received treatment without medical indication. Female patients were treated more often with betablockers and loop-diuretics than men. The percentage of nonsmokers was much higher in females. In an subgroup-analysis of 278 patients hospitalised because of acute decompensated heart failure OVD was not verifed in half of these individuals 6 months after discharge. Conclusion: In stable systolic HF, COPD is common but often misdiagnosed. Our data suggests that COPD in heart faulre is overestimated, probabyl due tue temporary OVD caused by pulmonal congestion. Spirometry and bodyplethysmography may help to differentiate between OVD and COPD and should be performed after cardial recompensation and before the beginning of an antiobstructive medical treatment.
KW  - Chronische Herzinsuffizienz
KW  - Herzinsuffizienz
KW  - Obstruktive Ventilationsstörung
KW  - Herzinsuffizienz
KW  - COPD
KW  - COPD
KW  - heart failure
KW  - gender
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-69781
ER  - 
TY  - JOUR
A1  - Eisele, Marion
A1  - Blozik, Eva
A1  - Störk, Stefan
A1  - Träder, Jens-Martin
A1  - Herrmann-Lingen, Christoph
A1  - Scherer, Martin
T1  - Recognition of depression and anxiety and their association with quality of life, hospitalization and mortality in primary care patients with heart failure - study protocol of a longitudinal observation study
JF  - BMC Family Practice
N2  - Background: International disease management guidelines recommend the regular assessment of depression and anxiety in heart failure patients. Currently there is little data on the effect of screening for depression and anxiety on the quality of life and the prognosis of heart failure (HF). We will investigate the association between the recognition of current depression/anxiety by the general practitioner (GP) and the quality of life and the patients' prognosis. 
Methods/Design: In this multicenter, prospective, observational study 3,950 patients with HF are recruited by general practices in Germany. The patients fill out questionnaires at baseline and 12-month follow-up. At baseline the GPs are interviewed regarding the somatic and psychological comorbidities of their patients. During the follow-up assessment, data on hospitalization and mortality are provided by the general practice. Based on baseline data, the patients are allocated into three observation groups: HF patients with depression and/or anxiety recognized by their GP (P+/+), those with depression and/or anxiety not recognized (P+/-) and patients without depression and/or anxiety (P-/-). We will perform multivariate regression models to investigate the influence of the recognition of depression and/or anxiety on quality of life at 12 month follow-up, as well as its influences on the prognosis (hospital admission, mortality). 
Discussion: We will display the frequency of GP-acknowledged depression and anxiety and the frequency of installed therapeutic strategies. We will also describe the frequency of depression and anxiety missed by the GP and the resulting treatment gap. Effects of correctly acknowledged and missed depression/anxiety on outcome, also in comparison to the outcome of subjects without depression/anxiety will be addressed. In case results suggest a treatment gap of depression/anxiety in patients with HF, the results of this study will provide methodological advice for the efficient planning of further interventional research.
KW  - anxiety
KW  - depression
KW  - health care research
KW  - heart failure
KW  - prevalence
KW  - observational study
KW  - prognosis
KW  - quality of life
KW  - hospitalization
KW  - treatment
KW  - mortality
KW  - task force
KW  - health questionnaire
KW  - cardiovascular care
KW  - validity
KW  - scale
KW  - validation
KW  - outcomes
KW  - standardization
KW  - population
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121881
SN  - 1471-2296
VL  - 14
IS  - 180
ER  - 
TY  - JOUR
A1  - Eiringhaus, Jörg
A1  - Wünsche, Christoph M.
A1  - Tirilomis, Petros
A1  - Herting, Jonas
A1  - Bork, Nadja
A1  - Nikolaev, Viacheslav O.
A1  - Hasenfuss, Gerd
A1  - Sossalla, Samuel
A1  - Fischer, Thomas H.
T1  - Sacubitrilat reduces pro‐arrhythmogenic sarcoplasmic reticulum Ca\(^{2+}\) leak in human ventricular cardiomyocytes of patients with end‐stage heart failure
JF  - ESC Heart Failure
N2  - Aims
Inhibition of neprilysin and angiotensin II receptor by sacubitril/valsartan (Val) (LCZ696) reduces mortality in heart failure (HF) patients compared with sole inhibition of renin–angiotensin system. Beneficial effects of increased natriuretic peptide levels upon neprilysin inhibition have been proposed, whereas direct effects of sacubitrilat (Sac) (LBQ657) on myocardial Ca\(^{2+}\) cycling remain elusive.

Methods and results
Confocal microscopy (Fluo‐4 AM) was used to investigate pro‐arrhythmogenic sarcoplasmic reticulum (SR) Ca\(^{2+}\) leak in freshly isolated murine and human ventricular cardiomyocytes (CMs) upon Sac (40 μmol/L)/Val (13 μmol/L) treatment. The concentrations of Sac and Val equalled plasma concentrations of LCZ696 treatment used in PARADIGM‐HF trial. Epifluorescence microscopy measurements (Fura‐2 AM) were performed to investigate effects on systolic Ca\(^{2+}\) release, SR Ca\(^{2+}\) load, and Ca\(^{2+}\)‐transient kinetics in freshly isolated murine ventricular CMs. The impact of Sac on myocardial contractility was evaluated using in toto‐isolated, isometrically twitching ventricular trabeculae from human hearts with end‐stage HF. Under basal conditions, the combination of Sac/Val did not influence diastolic Ca\(^{2+}\)‐spark frequency (CaSpF) nor pro‐arrhythmogenic SR Ca\(^{2}\) leak in isolated murine ventricular CMs (n CMs/hearts = 80/7 vs. 100/7, P = 0.91/0.99). In contrast, Sac/Val treatment reduced CaSpF by 35 ± 9% and SR Ca\(^{2+}\) leak by 45 ± 9% in CMs put under catecholaminergic stress (isoproterenol 30 nmol/L, n = 81/7 vs. 62/7, P < 0.001 each). This could be attributed to Sac, as sole Sac treatment also reduced both parameters by similar degrees (reduction of CaSpF by 57 ± 7% and SR Ca2+ leak by 76 ± 5%; n = 101/4 vs. 108/4, P < 0.01 each), whereas sole Val treatment did not. Systolic Ca2+ release, SR Ca\(^{2+}\) load, and Ca\(^{2+}\)‐transient kinetics including SERCA activity (k\(_{SERCA}\)) were not compromised by Sac in isolated murine CMs (n = 41/6 vs. 39/6). Importantly, the combination of Sac/Val and Sac alone also reduced diastolic CaSpF and SR Ca\(^{2+}\) leak (reduction by 74 ± 7%) in human left ventricular CMs from patients with end‐stage HF (n = 71/8 vs. 78/8, P < 0.05 each). Myocardial contractility of human ventricular trabeculae was not acutely affected by Sac treatment as the developed force remained unchanged over a time course of 30 min (n trabeculae/hearts = 3/3 vs. 4/3).

Conclusion
This study demonstrates that neprilysin inhibitor Sac directly improves Ca\(^{2+}\) homeostasis in human end‐stage HF by reducing pro‐arrhythmogenic SR Ca\(^{2+}\) leak without acutely affecting systolic Ca\(^{2+}\) release and inotropy. These effects might contribute to the mortality benefits observed in the PARADIGM‐HF trial.
KW  - heart failure
KW  - entresto
KW  - Neprilysin inhibition
KW  - Ca cycling
KW  - SR Ca leak
KW  - arrhythmia
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218479
VL  - 7
IS  - 5
SP  - 2992
EP  - 3002
ER  - 
TY  - JOUR
A1  - Drechsler, Christiane
A1  - Kolleritz, Barbara
A1  - Meinitzer, Andreas
A1  - März, Winfried
A1  - Ritz, Eberhard
A1  - König, Paul
A1  - Neyer, Ulrich
A1  - Pilz, Stefan
A1  - Wanner, Christoph
A1  - Kronenberg, Florian
T1  - Homoarginine and Progression of Chronic Kidney Disease: Results from the Mild to Moderate Kidney Disease Study
JF  - PLoS ONE
N2  - Background: Homoarginine is an amino acid derivative mainly synthesized in the kidney. It is suggested to increase nitric oxide availability, enhance endothelial function and to protect against cardiovascular diseases. We aimed to investigate the relation between homoarginine, kidney function and progression of chronic kidney disease (CKD). 
Methods: We measured plasma homoarginine concentrations in baseline samples of the Mild to Moderate Kidney Disease (MMKD) Study, a prospective cohort study of 227 patients with CKD in Europe. Homoarginine concentrations were available in 182 of the baseline samples and in 139 of the prospectively-followed patients. We correlated homoarginine concentrations to parameters of kidney function. The association between homoarginine and progression of CKD was assessed during a follow-up of up to seven years (median 4.45 years, interquartile range 2.54-5.19) using Cox regression analysis. Progression of CKD was defined as doubling of baseline serum creatinine and/or end-stage renal disease. 
Results: Study participants were at baseline on average 47 \(\pm\)13 years old and 65% were male. Mean \(\pm\) standard deviation of homoarginine concentrations were \(2.5 \pm 1.1 \mu mol/L\) and concentrations were incrementally lower at lower levels of GFR with mean concentrations of \(2.90 \pm 1.02 \mu mol/L\) (GFR. 90 ml/min), \(2.64 \pm 1.06 \mu mol/L\) (GFR 60-90 ml/min), \(2.52 \pm 1.24 \mu mol/L\) (GFR 30-60 ml/min) and \(2.05 \pm 0.78 \mu mol/L\) (GFR, 30 ml/min), respectively (p = 0.002). The age-and sex-adjusted risk to reach the renal endpoint was significantly higher by 62% with each decrease by one standard deviation (\(1.1 \mu mol/L\)) of homoarginine (HR 1.62, 95% CI 1.16-2.27, p = 0.005). This association was independent of proteinuria (HR 1.56, 95% CI 1.11-2.20, p = 0.01), and was slightly attenuated when adjusting for GFR (HR 1.40 (95% CI 0.98-1.98, p = 0.06). 
Conclusions: Homoarginine concentrations are directly correlated with kidney function and are significantly associated with the progression of CKD. Low homoarginine concentrations might be an early indicator of kidney failure and a potential target for the prevention of disease progression which needs further investigations.
KW  - risk
KW  - alkaline phosphatase
KW  - cardiovascular events
KW  - nictric-oxide
KW  - induced insulin-release
KW  - creatine synthesis
KW  - renal function
KW  - heart failure
KW  - rat kidney
KW  - L-arginine
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130979
VL  - 8
IS  - 5
ER  - 
TY  - THES
A1  - Boldt, Kristina
T1  - Vergleichende Untersuchung der prognostischen Relevanz von BNP, NT-proBNP, hsCRP und TNF-ɑ bei Patienten mit klinisch-anamnestischem Verdacht auf das Vorliegen einer Herzinsuffizienz in der Hausarztpraxis- : Follow-up-Untersuchung zur Grundstudie zur Objektivierung der kardiovaskulären Dysfunktion im ambulanten und hausärztlichen Bereich mittels handgehaltener Echokardiographie und dem BNP-Schnelltest (Handheld-BNP-Studie)
T1  - Prognostic utility of BNP, NT-proBNP, hsCRP and TNF-ɑ in the assessment of patients with suspected heart failure in primary care: The Handheld-BNP-Study
N2  - Herzinsuffizienz ist eine sehr häufige Erkrankung vor allem des höheren Lebensalters. Biomarker wie NT-proBNP, BNP, hsCRP haben neben ihrer Bedeutung für die Diagnose einer akuten Herzinsuffizienz einen großen Stellenwert in der Abschätzung der Prognose eines Patienten. Die prognostische Relevanz dieser Marker konnte auch bei nicht herzinsuffizienten, anderweitig kranken Patienten gezeigt werden. Unklar und wenig erforscht ist die Aussagekraft von Biomarkern in einem Kollektiv nicht akut dekompensierter Patienten, welche sich ambulant bei ihrem Hausarzt vorstellen. Die Handheld-BNP-Studie untersuchte im primärärztlichen Bereich das diagnostische Potential von BNP und der miniaturisierten Echokardiographie. Die vorliegende Follow-up-Studie untersucht die prognostische Relevanz von BNP sowie vergleichend den prognostischen Wert von NT-proBNP und der Kardiologendiagnose. Auch die prognostische Aussagekraft der inflammatorischen Marker hsCRP und TNF-ɑ, ebenso wie die Frage, ob durch eine Kombination der Marker die prognostische Abschätzung weiter gesteigerter werden kann, ist Gegenstand dieser Arbeit. Zuletzt wurde eine multivariate Regressionsanalyse durchgeführt, um den unabhängigen prognostischen Wert der Biomarker zu untersuchen. Es konnte gezeigt werden, dass bei diagnostisch naiven Patienten mit dem klinisch-anamnestischen Verdacht auf das Vorliegen einer Herzinsuffizienz das kardiale wie auch das nicht-kardiale Mortalitätsrisiko sowie die Rate an Hospitalisierungen gegenüber der Allgemeinbevölkerung gleichen Alters erhöht sind, unabhängig vom Vorliegen einer Herzinsuffizienz. Eine Bestimmung der Biomarker BNP, NT-proBNP, hsCRP und TNF-ɑ erwies sich in diesem Kollektiv als hilfreich, diejenigen mit erhöhtem Risiko zu erkennen.
N2  - Heart failure is a very common disease especially among old people. In addition to their importance for the diagnosis of acute heart failure, biomarkers such as NT-proBNP, BNP, hsCRP and TNF-ɑ play a major role in the assessment of patients prognosis. The prognostic relevance of these markers could even be demonstrated on ill patients with a diagnosis other than heart failure. The significance of biomarkers in a group of not acutely decompensated patients, who consult their general practitioner, is unclear and little explored. The Handheld-BNP-study examined the diagnostic potential of BNP an the miniaturized echokardiography in a primary care setting. The follow-up-study at hand investigates the prognostic relevance of BNP and compares the prognostic value of NT-proBNP and the cardiologist diagnosis. The prognostic value of the inflammatory markers hsCRP and TNF-ɑ, as well as the question of wether the prognostic assessment can further be enhanced by a combination af these markers, are subject of this thesis. At last, a multivariate regression analysis was performed to investigate the independent prognostic value of biomarkers. The thesis shows that the cardiac and non-cardiac mortality risk and the hospitalization rate in diagnostically naive patients with diffuse symptoms who are potentially indicative of heart failure is high, compared to other people of similar age, irrespective of the presence of heart failure. A determination of the biomarkers BNP, NT-proBNP, hsCRP and TNF-ɑ in this cohort proved to be helpful to identify those at increased risk.
KW  - BNP
KW  - NT-proBNP
KW  - Herzinsuffizienz
KW  - Prognose
KW  - Hausarzt
KW  - BNP
KW  - NT-proBNP
KW  - Herzinsuffizienz
KW  - Hausarzt
KW  - Prognose
KW  - BNP
KW  - NT-proBNP
KW  - heart failure
KW  - primary care
KW  - prognosis
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-65088
ER  -