TY - JOUR A1 - Altieri, Barbara A1 - La Salvia, Anna A1 - Modica, Roberta A1 - Marciello, Francesca A1 - Mercier, Olaf A1 - Filosso, Pier Luigi A1 - de Latour, Bertrand Richard A1 - Giuffrida, Dario A1 - Campione, Severo A1 - Guggino, Gianluca A1 - Fadel, Elie A1 - Papotti, Mauro A1 - Colao, Annamaria A1 - Scoazec, Jean-Yves A1 - Baudin, Eric A1 - Faggiano, Antongiulio T1 - Recurrence-free survival in early and locally advanced large cell neuroendocrine carcinoma of the lung after complete tumor resection JF - Journal of Personalized Medicine N2 - Background: Large Cell Neuroendocrine Carcinoma (LCNEC) is a rare subtype of lung cancer with poor clinical outcomes. Data on recurrence-free survival (RFS) in early and locally advanced pure LCNEC after complete resection (R0) are lacking. This study aims to evaluate clinical outcomes in this subgroup of patients and to identify potential prognostic markers. Methods: Retrospective multicenter study including patients with pure LCNEC stage I-III and R0 resection. Clinicopathological characteristics, RFS, and disease-specific survival (DSS) were evaluated. Univariate and multivariate analyses were performed. Results: 39 patients (M:F = 26:13), with a median age of 64 years (44–83), were included. Lobectomy (69.2%), bilobectomy (5.1%), pneumonectomy (18%), and wedge resection (7.7%) were performed mostly associated with lymphadenectomy. Adjuvant therapy included platinum-based chemotherapy and/or radiotherapy in 58.9% of cases. After a median follow-up of 44 (4–169) months, the median RFS was 39 months with 1-, 2- and 5-year RFS rates of 60.0%, 54.6%, and 44.9%, respectively. Median DSS was 72 months with a 1-, 2- and 5-year rate of 86.8, 75.9, and 57.4%, respectively. At multivariate analysis, age (cut-off 65 years old) and pN status were independent prognostic factors for both RFS (HR = 4.19, 95%CI = 1.46–12.07, p = 0.008 and HR = 13.56, 95%CI 2.45–74.89, p = 0.003, respectively) and DSS (HR = 9.30, 95%CI 2.23–38.83, p = 0.002 and HR = 11.88, 95%CI 2.28–61.84, p = 0.003, respectively). Conclusion: After R0 resection of LCNEC, half of the patients recurred mostly within the first two years of follow-up. Age and lymph node metastasis could help to stratify patients for adjuvant therapy. KW - neuroendocrine tumor KW - LCNEC KW - pulmonary cancer KW - prognostic marker KW - prognosis KW - survival KW - lymph nodes KW - age KW - surgery KW - adjuvant therapy Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304000 SN - 2075-4426 VL - 13 IS - 2 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 - TY - JOUR A1 - Chifu, Irina A1 - Heinze, Britta A1 - Fuss, Carmina T. A1 - Lang, Katharina A1 - Kroiss, Matthias A1 - Kircher, Stefan A1 - Ronchi, Cristina L. A1 - Altieri, Barbara A1 - Schirbel, Andreas A1 - Fassnacht, Martin A1 - Hahner, Stefanie T1 - Impact of the Chemokine Receptors CXCR4 and CXCR7 on Clinical Outcome in Adrenocortical Carcinoma JF - Frontiers in Endocrinology N2 - Chemokine receptors have a negative impact on tumor progression in several human cancers and have therefore been of interest for molecular imaging and targeted therapy. However, their clinical and prognostic significance in adrenocortical carcinoma (ACC) is unknown. The aim of this study was to evaluate the chemokine receptor profile in ACC and to analyse its association with clinicopathological characteristics and clinical outcome. A chemokine receptor profile was initially evaluated by quantitative PCR in 4 normal adrenals, 18 ACC samples and human ACC cell line NCI-H295. High expression of CXCR4 and CXCR7 in both healthy and malignant adrenal tissue and ACC cells was confirmed. In the next step, we analyzed the expression and cellular localization of CXCR4 and CXCR7 in ACC by immunohistochemistry in 187 and 84 samples, respectively. These results were correlated with clinicopathological parameters and survival outcome. We detected strong membrane expression of CXCR4 and CXCR7 in 50% of ACC samples. Strong cytoplasmic CXCR4 staining was more frequent among samples derived from metastases compared to primaries (p=0.01) and local recurrences (p=0.04). CXCR4 membrane staining positively correlated with proliferation index Ki67 (r=0.17, p=0.028). CXCR7 membrane staining negatively correlated with Ki67 (r=−0.254, p=0.03) but positively with tumor size (r=0.3, p=0.02). No differences in progression-free or overall survival were observed between patients with strong and weak staining intensities for CXCR4 or CXCR7. Taken together, high expression of CXCR4 and CXCR7 in both local tumors and metastases suggests that some ACC patients might benefit from CXCR4/CXCR7-targeted therapy. KW - chemokine receptor KW - prognosis KW - adrenocortical carcinoma KW - CXCR4 KW - CXCR7 Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-216494 SN - 1664-2392 VL - 11 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 - Lippert, Juliane A1 - Fassnacht, Martin A1 - Ronchi, Cristina L. T1 - The role of molecular profiling in adrenocortical carcinoma JF - Clinical Endocrinology N2 - Adrenocortical carcinoma (ACC) is a rare, aggressive cancer with still partially unknown pathogenesis, heterogenous clinical behaviour and no effective treatment for advanced stages. Therefore, there is an urgent clinical unmet need for better prognostication strategies, innovative therapies and significant improvement of the management of the individual patients. In this review, we summarize available studies on molecular prognostic markers and markers predictive of response to standard therapies as well as newly proposed drug targets in sporadic ACC. We include in vitro studies and available clinical trials, focusing on alterations at the DNA, RNA and epigenetic levels. We also discuss the potential of biomarkers to be implemented in a clinical routine workflow for improved ACC patient care. KW - adrenocortical cancer KW - biomarkers KW - precision medicine KW - prognosis KW - targeted treatment Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258382 VL - 97 IS - 4 ER - TY - JOUR A1 - Liu, Dan A1 - Hu, Kai A1 - Lau, Kolja A1 - Kiwitz, Tobias A1 - Robitzkat, Katharina A1 - Hammel, Clara A1 - Lengenfelder, Björn Daniel A1 - Ertl, Georg A1 - Frantz, Stefan A1 - Nordbeck, Peter T1 - Impact of diastolic dysfunction on outcome in heart failure patients with mid-range or reduced ejection fraction JF - ESC Heart Failure N2 - Aims The role of diastolic dysfunction (DD) in prognostic evaluation in heart failure (HF) patients with impaired systolic function remains unclear. We investigated the impact of echocardiography-defined DD on survival in HF patients with mid-range (HFmrEF, EF 41–49%) and reduced ejection fraction (HFrEF, EF < 40%). Methods and results A total of 2018 consecutive hospitalized HF patients were retrospectively included and divided in two groups based on baseline EF: HFmrEF group (n = 951, aged 69 ± 13 years, 74.2% male) and HFrEF group (n = 1067, aged 68 ± 13 years, 76.3% male). Clinical data were collected and analysed. All patients completed ≥1 year clinical follow-up. The primary endpoint was defined as all-cause death (including heart transplantation) and cardiovascular (CV)-related death. All-cause mortality (30.8% vs. 24.9%, P = 0.003) and CV mortality (19.1% vs. 13.5%, P = 0.001) were significantly higher in the HFrEF group than the HFmrEF group during follow-up [median 24 (13–36) months]. All-cause mortality increased in proportion to DD severity (mild, moderate, and severe) in either HFmrEF (17.1%, 25.4%, and 37.0%, P < 0.001) or HFrEF (18.9%, 30.3%, and 39.2%, P < 0.001) patients. The risk of all-cause mortality [hazard ratio (HR) = 1.347, P = 0.015] and CV mortality (HR = 1.508, P = 0.007) was significantly higher in HFrEF patients with severe DD compared with non-severe DD after adjustment for identified clinical and echocardiographic covariates. For HFmrEF patients, severe DD was independently associated with increased all-cause mortality (HR = 1.358, P = 0.046) but not with CV mortality (HR = 1.155, P = 0.469). Conclusions Echocardiography-defined severe DD is independently associated with increased all-cause mortality in patients with HFmrEF and HFrEF. KW - heart failure with mid-range ejection fraction KW - heart failure with reduced ejection fraction KW - diastolic dysfunction KW - echocardiography KW - prognosis Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258894 VL - 8 IS - 4 ER - TY - JOUR A1 - Liu, Dan A1 - Hu, Kai A1 - Niemann, Markus A1 - Herrmann, Sebastian A1 - Cikes, Maja A1 - Störk, Stefan A1 - Beer, Meinrad A1 - Gaudron, Philipp Daniel A1 - Morbach, Caroline A1 - Knop, Stefan A1 - Geissinger, Eva A1 - Ertl, Georg A1 - Bijnens, Bart A1 - Weidemann, Frank T1 - Impact of Regional Left Ventricular Function on Outcome for Patients with AL Amyloidosis JF - PLoS ONE N2 - Objectives The aim of this study was to explore the left ventricular (LV) deformation changes and the potential impact of deformation on outcome in patients with proven light-chain (AL) amyloidosis and LV hypertrophy. Background Cardiac involvement in AL amyloidosis patients is associated with poor outcome. Detecting regional cardiac function by advanced non-invasive techniques might be favorable for predicting outcome. Methods LV longitudinal, circumferential and radial peak systolic strains (Ssys) were assessed by speckle tracking imaging (STI) in 44 biopsy-proven systemic AL amyloidosis patients with LV hypertrophy (CA) and in 30 normal controls. Patients were divided into compensated (n = 18) and decompensated (n = 26) group based on clinical assessment and followed-up for a median period of 345 days. Results Ejection fraction (EF) was preserved while longitudinal Ssys (LSsys) was significantly reduced in both compensated and decompensated groups. Survival was significantly reduced in decompensated group (35% vs. compensated 78%, P = 0.001). LSsys were similar in apical segments and significantly reduced in basal segments between two patient groups. LSsys at mid-segments were significantly reduced in all LV walls of decompensated group. Patients were further divided into 4 subgroups according to the presence or absence of reduced LSsys in no (normal), only basal (mild), basal and mid (intermediate) and all segments of the septum (severe). This staging revealed continuously worse prognosis in proportion to increasing number of segments with reduced LSsys (mortality: normal 14%, mild 27%, intermediate 67%, and severe 64%). Mid-septum LSsys<11% suggested a 4.8-fold mortality risk than mid-septum LSsys≥11%. Multivariate regression analysis showed NYHA class and mid-septum LSsys were independent predictors for survival. Conclusions Reduced deformation at mid-septum is associated with worse prognosis in systemic amyloidosis patients with LV hypertrophy. KW - regression analysis KW - ejection fraction KW - echocardiography KW - cardiac transplantation KW - deformation KW - amyloidosis KW - prognosis KW - stem cell transplantation Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130293 VL - 8 IS - 3 ER - TY - JOUR A1 - Liu, Dan A1 - Hu, Kai A1 - Störk, Stefan A1 - Herrmann, Sebastian A1 - Kramer, Bastian A1 - Cikes, Maja A1 - Gaudron, Philipp Daniel A1 - Knop, Stefan A1 - Ertl, Georg A1 - Bijnens, Bart A1 - Weidemann, Frank T1 - Predictive Value of Assessing Diastolic Strain Rate on Survival in Cardiac Amyloidosis Patients with Preserved Ejection Fraction JF - PLOS ONE N2 - Objectives: Since diastolic abnormalities are typical findings of cardiac amyloidosis (CA), we hypothesized that speckle-tracking-imaging (STI) derived longitudinal early diastolic strain rate (LSRdias) could predict outcome in CA patients with preserved left ventricular ejection fraction (LVEF >50%). Background: Diastolic abnormalities including altered early filling are typical findings and are related to outcome in CA patients. Reduced longitudinal systolic strain (LSsys) assessed by STI predicts increased mortality in CA patients. It remains unknown if LSRdias also related to outcome in these patients. Methods: Conventional echocardiography and STI were performed in 41 CA patients with preserved LVEF (25 male; mean age 65±9 years). Global and segmental LSsys and LSRdias were obtained in six LV segments from apical 4-chamber views. Results: Nineteen (46%) out of 41 CA patients died during a median of 16 months (quartiles 5–35 months) follow-up. Baseline mitral annular plane systolic excursion (MAPSE, 6±2 vs. 8±3 mm), global LSRdias and basal-septal LSRdias were significantly lower in non-survivors than in survivors (all p<0.05). NYHA class, number of non-cardiac organs involved, MAPSE, mid-septal LSsys, global LSRdias, basal-septal LSRdias and E/LSRdias were the univariable predictors of all-cause death. Multivariable analysis showed that number of non-cardiac organs involved (hazard ratio [HR] = 1.96, 95% confidence interval [CI] 1.17–3.26, P = 0.010), global LSRdias (HR = 7.30, 95% CI 2.08–25.65, P = 0.002), and E/LSRdias (HR = 2.98, 95% CI 1.54–5.79, P = 0.001) remained independently predictive of increased mortality risk. The prognostic performance of global LSRdias was optimal at a cutoff value of 0.85 S−1 (sensitivity 68%, specificity 67%). Global LSRdias <0.85 S−1 predicted a 4-fold increased mortality in CA patients with preserved LVEF. Conclusions: STI-derived early diastolic strain rate is a powerful independent predictor of survival in CA patients with preserved LVEF. KW - diagnostic medicine KW - echocardiography KW - prognosis KW - calcium imaging KW - ejection fraction KW - death rates KW - amyloidosis KW - deformation Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-118024 SN - 1932-6203 VL - 9 IS - 12 ER - TY - THES A1 - Steimann, Iris T1 - Effekt von Pharmakotherapie und Komorbidität auf die Prognose chronisch herzinsuffizienter Patienten - eine prospektive Kohortenstudie T1 - Effect of pharmacotherapy and comorbidity on the prognosis of patients with chronic heart failure - a prospective cohort study N2 - Die chronische Herzinsuffizienz ist eine sehr häufige Erkrankung des höheren Lebensalters und eine der wichtigsten Todesursachen in den Industrienationen. Die Prognose der chronischen Herzinsuffizienz konnte durch Einführung einer Therapie mit ACE-Hemmern/AT1-Antagonisten und Betablockern deutlich verbessert werden. Allerdings wurde die Effektivität einer leitliniengerechten Pharmakotherapie der chronischen Herzinsuffizienz bisher nicht nachgewiesen. Ziel der vorliegenden prospektiven Kohortenstudie war es, diesen Effekt auf den Tod jeder Ursache, je nach Grad der Einhaltung der leitliniengerechten Pharmakotherapie, in einem konsekutiven Kollektiv chronisch herzinsuffizienter Patienten unter Berücksichtigung der Komorbidität zu bestimmen. Im Zeitraum von 2002-2003 wurden 1054 stationäre oder ambulante Pa-tienten mit chronischer Herzinsuffizienz jeder Ätiologie und jeden Schweregra-des konsekutiv in die Studie aufgenommen und über im Mittel 2 Jahre nachbeobachtet. Alle Patienten wurden detailliert klinisch, laborchemisch und echokardiographisch charakterisiert: das mediane Alter betrug 71,8 Jahre, 60% der Patienten waren männlich und 61% der Patienten hatten eine reduzierte und 39% eine erhaltene linksventrikuläre systolische Funktion. Der Grad der leitliniengerechten Pharmakotherapie (GLT) wurde gemäß der MAHLER Studie berechnet, um die Qualität der Pharmakotherapie zu mes-sen. Er basierte auf der Verschreibung von ACE-Hemmern/AT1-Antagonisten, Betablockern und Mineralkortikoid-Rezeptorblockern (GLT-3), die gemäß der Europäischen Leitlinien für die Behandlung der chronischen Herzinsuffizienz empfohlen sind. Zudem wurde der GLT-5 berechnet, der zusätzlich die Medikation mit Diuretika und Herzglykosiden berücksichtigte. Bei Patienten mit reduzierter linksventrikulärer systolischer Funktion betrug der mediane GLT-3 67%. Er war invers assoziiert mit dem Alter, der NYHA Klasse und der Häufigkeit der Komorbiditäten. In den Kategorien „niedrig“, „mittel“ und „hoch“ ergaben sich für den GLT-3 Mortalitätsraten von 79, 30 und 11 pro 100 Patientenjahre Follow-up. In der multivariablen Cox-Regressionsanalyse war ein hoher vs. niedriger GLT-3 ein unabhängiger Prä-diktor für ein niedrigeres Mortalitätsrisiko: Hazard Rate 0,50, 95%Konfidenzintervall (KI) 0,32-0,74, P<0,001. Außerdem blieb ein hoher GLT-3 bei Patienten höheren Alters (HR 0,42, 95%KI 0,27-0,66; P<0,001) und bei Frauen (HR 0,42, 95%KI 0,23-0,79; P=0,007) mit einem niedrigeren Mortalitätsrisiko assoziiert. Obwohl es bisher keine evidenzbasierten Leitlinien für Patienten mit erhaltener linksventrikulärer systolischer Funktion gibt, wurden diese im klinischen Alltag ähnlich behandelt wie Patienten mit reduzierter linksventrikulärer systolischer Funktion. Sie profitierten in unserer Studie von dieser Therapie in einem ähnlichen Maße wie Patienten mit reduzierter linksventrikulärer systolischer Funktion (HR 0,37, 95%KI 0,21-0,66, P<0,001). Zusammenfassend war in diesem konsekutiven Kollektiv eine leitlinien-gerechte Pharmakotherapie mit einer deutlich besseren Prognose der chroni-schen Herzinsuffizienz mit reduzierter linksventrikulärer systolischer Funktion assoziiert, unabhängig von Alter oder Geschlecht. Eine ähnliche Verbesserung der Prognose konnte auch bei Patienten mit erhaltener linksventrikulärer systolischer Funktion nachgewiesen werden. N2 - The syndrome of heart failure (CHF) is common in elderly persons and a main contributor to cardiovascular morbidity and mortality worldwide. The prognosis of heart failure has been considerably improved since the implementation of angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor type-1 blockers (ARB) and betablockers. So far, however, the effectiveness of adherence to current treatment guidelines has not been proven. The objective of this prospective cohort study was to estimate the effect of adherence to pharmacotherapeutic recommendations on all-cause death in non-selected patients with chronic heart failure. During the June 2002 and December 2003, 1,054 in- and outpatients with heart failure of any cause and severity were consecutively included and were followed over 2.5 years. All patients were characterized in detail regarding history, physical examination, medication, laboratory assessment, electro- and echocardiography. The guideline adherence indicator (GAI) was calculated according to the MAHLER study to measure the quality of the pharmacotherapy. The main analyses was based on the GAI-3 which comprised the three substance classes for which the best evidence from randomized trials is available: ACE inhibitors/ARB, betablockers and mineral receptor antagonists: In addition, the GAI-5 was calculated, which considered, in addition, the prescription of diuretics and cardiac glycosides. The mean age was 71.6 years, 60% of the patients were male, 61% exhibited a reduced and 39% a preserved left ventricular ejection fraction (LVEF). In patients with reduced LVEF, the median GLT-3 was 67%. It was inversely associated with age, New York Heart Association functional class, and the frequency of important comorbidities. Grouping GAI-3 into low, medium and high categories, the total mortality rates were 79, 30, and 11 per 100 person-years of follow-up, respectively. In multivariable Cox regression, high GAI-3 was independently predictive of lower mortality risk: hazard ratio (HR) 0.50 (95% confidence interval [CI] 0.32-0.74; P<0.001) vs. low GAI-3. Moreover, a high GAI-3 remained associated with lower total mortality risk in patients of high age (HR 0.42, 95%CI 0.27-0.66; P<0.001) and in females (HR 0.42, 95%CI 0.23-0.79; P=0.007). Despite lacking evidence-based guidelines for patients with preserved LVEF, in clinical practice, they were treated similarly to patients with reduced LVEF, and they seemed to benefit to a comparable extent (HR 0.37, 95%CI 0.21-0.66, P<0.001). In conclusion, in this community based cohort, better adherence to treatment guidelines was independently associated with a considerably improved prognosis in patients with heart failure and a reduced LVEF. These benefits were also apparent in old patients and women. Comparable effects were observed in patients with preserved LVEF. KW - Pharmakotherapie KW - Langfristige Prognose KW - Chronische Herzinsuffizienz KW - Sekundärkrankheit KW - Sterblichkeit KW - Kohortenstudie KW - leitliniengerechte Pharmakotherapie KW - Patientencharakteristika KW - prospektive Studie KW - prognosis KW - guideline adherence KW - comorbidity KW - chronic heart failure KW - cohort study Y1 - 2009 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-36229 ER - TY - JOUR A1 - Weidemann, F. A1 - Niemann, M. A1 - Stork, S. A1 - Breunig, F. A1 - Beer, M. A1 - Sommer, C. A1 - Herrmann, S. A1 - Ertl, G. A1 - Wanner, C. T1 - Long-term outcome of enzyme-replacement therapy in advanced Fabry disease: evidence for disease progression towards serious complications JF - Journal of Internal Medicine N2 - The long-term effects of enzyme-replacement therapy (ERT) in Fabry disease are unknown. Thus, the aim of this study was to determine whether ERT in patients with advanced Fabry disease affects progression towards 'hard' clinical end-points in comparison with the natural course of the disease. METHODS: A total of 40 patients with genetically proven Fabry disease (mean age 40 ± 9 years; n = 9 women) were treated prospectively with ERT for 6 years. In addition, 40 subjects from the Fabry Registry, matched for age, sex, chronic kidney disease stage and previous transient ischaemic attack (TIA), served as a comparison group. The main outcome was a composite of stroke, end-stage renal disease (ESRD) and death. Secondary outcomes included changes in myocardial left ventricular (LV) wall thickness and replacement fibrosis, change in glomerular filtration rate (GFR), new TIA and change in neuropathic pain. RESULTS: During a median follow-up of 6.0 years (bottom and top quartiles: 5.1, 7.2), 15 events occurred in 13 patients (n = 7 deaths, n = 4 cases of ESRD and n = 4 strokes). Sudden death occurred (n = 6) only in patients with documented ventricular tachycardia and myocardial replacement fibrosis. The annual progression of myocardial LV fibrosis in the entire cohort was 0.6 ± 0.7%. As a result, posterior end-diastolic wall thinning was observed (baseline, 13.2 ± 2.0 mm; follow-up, 11.4 ± 2.1 mm; P < 0.01). GFR decreased by 2.3 ± 4.6 mL min(-1) per year. Three patients experienced a TIA. The major clinical symptom was neuropathic pain (n = 37), and this symptom improved in 25 patients. The event rate was not different between the ERT group and the untreated (natural history) group of the Fabry Registry. CONCLUSION: Despite ERT, clinically meaningful events including sudden cardiac death continue to develop in patients with advanced Fabry disease. KW - Fabry disease KW - α-galactosidase A KW - dialysis KW - prognosis KW - stroke KW - sudden cardiac death Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132075 VL - 247 IS - 4 ER -